Best Practices For Maintaining A Blind In Biosimilar Clinical Trials

By Anna Rose Welch, Editorial & Community Director, Advancing RNA

Unlike novel biologics, a biosimilar candidate has a shortened clinical development process involving only Phase 1 and Phase 3 trials. The obvious benefit is that this abbreviated clinical pathway gives a biosimilar candidate earlier access to the market. But because of this aggressive timeline, it becomes more difficult to ensure that clinical trial personnel running biosimilar trials clearly understand their roles and responsibilities, especially when it comes to maintaining a blind.

What Are The Biggest Biosimilar Blinding Challenges?

I recently had the opportunity to sit in on a webinar held by Fisher Clinical Services. The webinar began with a polling question, posed by Fisher Clinical expert Dan Ramos. He gave all participants the opportunity to select one of four answers to the question, “What do you see as being the largest blinding challenge in biosimilar clinical trials?”

Nearly 50 percent of participants claimed their biggest challenge was the use of non-blinded staff for drug administration, followed by 26 percent who found the unclear clinical staff roles and responsibilities most challenging. There were also issues with electronic communications, including web portals and public email hosts (9 percent), and improper dissemination of operational documents (18 percent).

How Does Unblinding Occur?

In biosimilar trials in particular, there are several factors that complicate blinding. For one, many popular biologics, such as the widely used Humira, come to market in prefilled syringes, which are easily recognizable. Accidental unblinding can also occur when certain documents, including randomization lists, packaging lists, invoices, and reports from quality assurance, are shared, in turn, revealing treatment assignments. Though it’s rare that medical staff would share a randomization list, for instance, with blinded physicians and other colleagues, Ramos emphasizes there is always a risk. It’s best to be aware of these risks when planning and managing a blinded biosimilar (or any blinded) clinical trial.

What Can Be Done To Address These Challenges?

Ramos presented a few strategies to address the specific challenges that might arise in a biosimilar trial. For one, when it comes to having a biologic with a recognizable device, he said, “One option could be to supply a matching syringe with overlabeling for the originator product. A company could also prepare both the originator and biosimilar at the study site, administering to blinded patients and blinded pharmacists.”

However, while these could be great solutions for the aforementioned problems, it’s important to take a step back and look at the bigger picture. In the manufacturing space, there’s the concept of root cause analysis. Often a company will correct issues, only to find the same problem keeps recurring. This problem continues to rear its head because the company has not yet determined its root cause. Therefore, at the base level, there needs to be an overall understanding of who knows what in an organization in order to maintain a blind in clinical trials.

As Ramos’ poll question revealed, biosimilar sponsors find it particularly challenging to ensure all personnel understand the roles and responsibilities they have within the organization. “Make sure that people are aware of what information they’re accountable for,” Ramos explained. “All personnel need to know who is blinded and who is not.” This transparency also carries over to a company’s vendors. There is a chance distribution or shipping documentation could land in the wrong hands. As such, it’s important every organization is aware of the information being passed around within their walls or being shared by vendors.

One of the best ways to clarify which members of the staff are blinded/unblinded, Ramos suggests, is to use a blinding procedures checklist, also known as a responsibility assignment matrix (RACI). This document shows a breakdown of all the blinded personnel, the contact in case there is an emergency unblinding, as well as who has the authority to unblind a study. Ramos said, “Understanding who to contact and knowing who has this key information is a critical factor for the success of your clinical trial.”