When Clinical Trial Blinding Becomes Impossible, Virtual Placebo Groups Offer a Solution

Increasingly, sharing of information online through social media has made blinding of placebo groups in clinical trials virtually impossible. In some disease states, particularly multiple sclerosis, virtual placebo groups may offer a solution.

When it comes to validating the efficacy of a new drug, double-blind trials have been a standard of research since 1944, when HP Himsworth and colleagues conducted what is widely believed to be the first double-blind placebo-controlled trial.¹ The world has changed since that milestone 70 years ago, and social media is beginning to make placebo-group blinding virtually impossible.²

Facebook, forums, and blogs enable patients in a trial to communicate, which potentially allows patients to recognize when they are receiving a placebo. On social media, patients can swap information about how to get into trials, even when they are not eligible.

For manufacturers and regulators, the danger of this information sharing is inaccurate reporting of adverse events and use of drugs that may be inappropriate for certain groups of patients.

For example, if a drug is known to be dangerous for patients with chronic migraines, a trial may exclude patients with a history of chronic migraines. Patients who become aware of this exclusion criterion may then advise others to hide their chronic migraine condition to avoid being excluded from the study. As a result of improper patient selection, adverse events may occur in the study that could halt drug development.

In other cases, misinformation that may harm patients can spread through the internet. For instance, patients could be ill-advised not to report symptoms to avoid dropping out of a trial.

Bloggers enrolled in clinical trials may also report their experience with a given drug. In 1 instance, a women taking a medication for multiple sclerosis reported her experiences with the treatment on a blog. Sharing that information potentially offered false hope for patients with anecdotal evidence that may be a result of coincidental disease severity fluctuations, and not due to the use of medication.²

The sharing of information on social media is a challenge for both manufacturers and regulators. Food and Drug Administration (FDA) officials acknowledge the positive aspects of interpatient communication, which can improve understanding of a disease. The FDA has not yet placed any regulations on communication between patients in the context of a clinical trial. Spokespeople for the FDA, however, indicate that officials are aware of the issues caused by uncontrolled information sharing.²

In many life-threatening, chronic conditions, such as multiple sclerosis, patients may feel that they have a right to know if they are getting the active drug or a placebo. Some critics of placebo-controlled trials claim that historical cohorts for comparison may be a more appropriate way to conduct certain types of trials.³

Researchers at the Human Motion Institute in Munich, Germany have suggested that, because the etiology and disease course of multiple sclerosis is now well understood, placebo groups in clinical trials of new multiple sclerosis drugs should be replaced with "virtual placebo groups."³

A virtual placebo group is composed of virtual patients who are matched to real patients based on mathematical and statistical methods using historical information. One such database of patients with multiple sclerosis includes more than 100,000 patient-years of information from approximately 26,000 patients.³

Not only would this mathematical strategy eliminate the need for potentially unethical use of placebo in patients with multiple sclerosis who need treatment, but proponents of virtual placebo groups argue that results of such trials would offer better information. Virtual patients could be better matched to existing patients in trials. This matching procedure, termed robust prognostic matching, would virtually eliminate the influence of baseline differences between placebo and treatment groups.³

Given that placebo groups are increasingly aware that they are not receiving active treatment, virtual placebo groups may be 1 solution to the ethical dilemma of withholding treatment and the increasing influence of social media on clinical trials.

References:

• Patulin Clinical Trials Committee, Medical Research Council. Clinical trial of patulin in the common cold. 1944. Int J Epidemiol. 2004;33(2):243-246.
• Marcus AD. Researchers Fret as Social Media Lift Veil on Drug Trials. Wall Street Journal. Published July 29, 2014. Accessed July 31, 2014.
• Daumer H, Lederer C. Robust prognostic matching — do virtual placebo groups solve the placebo problem in multiple sclerosis research? The Human Motion Institute. http://www.dresdnerpalaisgespraeche.de/ha/_data/Daumer_HA_16_Robust_Prognostic_Matching-EN-CL.pdf. Accessed July 31, 2014.