I’m being unblinded?!
Explaining the patient experience at HBRF
Earlier this month, the team at Hope Biosciences Research Foundation (HBRF) successfully closed an FDA-authorized Phase II, double-blind, placebo controlled clinical trial in Multiple Sclerosis (MS), which means we now move to unblinding. We were excited to share this milestone with participants and stakeholders, but quickly realized “clinical trial jargon” can insert confusion into even the best news. In the spirit of clarity and without further ado, here’s a crash course in blinding-related terminology — so when we call you, you’ll be as excited as we are.
Key terms, explained
Double-blind, placebo-controlled randomized clinical trials are a gold standard of evidence-based practice in clinical research, and much of the work conducted at HBRF is of this kind. All processes are undertaken in accordance with Good Clinical Practice, an international ethical and scientific quality standard for designing, conducting, recording and reporting trials in human subjects.
“Placebo controlled” means that some percentage (usually half) of clinical trial participants receive the drug under investigation, while the remainder (usually half) receive a placebo.[1] Patients are “randomized” as they begin treatment. That is, patients are assigned to a group in a seemingly random manner that cannot be readily predicted; patients are not, for instance, assigned to groups in an “A, B, A, B” or any other pattern they or clinical staff might be able to discern. Randomization is one component of blinding. “Blinding” means just that — masking from one or more parties involved in a research protocol to information that might bias results, including knowledge of specific participants receiving the investigational product and/or a placebo. A “double blinded” protocol demands that both participants and those administering the treatment remain in the proverbial dark about which patients, are in which group. Entities that must remain blinded for the duration of the protocol include clinical trial participants and their families and caregivers, the clinical staff administering treatment, members of the safety data and monitoring committees, and statisticians, scientists, manuscript writers, and anyone else involved in analyzing data and interpreting outcomes.
“Closing” a study is a milestone that means all patients have been treated and all data has been gathered — the study is “closed” to additional information. Once a clinical trial is closed, the sponsoring organization analyzes the data in earnest, drawing conclusions and preparing to share their findings with the world. Also at this time, the sponsoring organization is free to inform clinical trial participants whether they were in the “treatment” group and received the investigational product, or if they were in the “placebo” group and did not. HBRF prefers to unblind individuals on a strictly need-to-know basis. The designated patient liaison, for example, needs to be unblinded early in the process to share information with patients; the statisticians and manuscript writers, who may work through edits and future iterations of their work in the weeks or months to come, do not.
Inclusion in a double-blinded, placebo controlled clinical trial can spark many emotions in participants. Over the course of a clinical trial countless conversations take place between caregivers, families, and participants about whether they think they are receiving treatment or not. Future care decisions may be deferred pending results of the clinical trial, especially if participants observe visible positive changes in themselves or other members of the patient group. As a clinical research team we, too, are extremely relieved when a study closes and it’s time to inform participants.
Except when we call with news, leave excited voicemails, and no one calls us back. Ghosted?! What is going on?!
The unblinding experience
Turns out, the term “unblinding” is not one heard every day in coffee shops, libraries, or community events, and folks aren’t always sure how to feel when they get a voicemail, email, or other communique informing them they have been “unblinded.” “Unblinding” simply means revealing the previously withheld information; in this case, what treatment group you were in.
A few more things to know about the process:
· Every clinical research organization has their own process for unblinding, as approved by FDA in initial protocol submission. At HBRF, we reach you the most personal way possible — if you are local to Sugar Land, we typically ask for an in-person. For participants living in other locations, a video conference is arranged. We want to honor the personal nature of an unblinding occasion, while providing ample opportunity to answer questions that may arise based on the new information shared in unblinding.
· When appropriate and if the original study demonstrates statistically significant results, HBRF petitions for treatment of the placebo group through the Expanded Access Program. Timelines to treatment vary widely, when they occur, and must be authorized by FDA.
We hope this conversation instills a sense of calm in your clinical trial experience, or adds an element of clarity to your decision-making process if you have yet to participate in clinical research.
Bottom line: if HBRF ever calls you or a loved one to schedule an unblinding meeting, please pick up the phone! We are excited beyond words to speak and walk with you, whatever the next steps in this journey are for you and yours. Thank you for trusting us. Thank you for being here.
[1] The most common study design publicized on clinicaltrials.gov calls for two groups — one receives treatment, one does not — but studies with three or more groups are also commonly employed. In these designs, one group typically receives placebo and the remainder receive variations of the drug or therapy, which might include differences in dosing strength, periodicity of drug administration, or how the drug is administered.
