SYDNEY, Australia — The use of a placebo in randomized controlled trials of new treatments for Parkinson's disease (PD) reduces the measured efficacy of active treatments, novel research suggests.

"We use placebo to quantify the therapeutic benefit a patient experiences from the mere expectation of benefit from being given a therapeutic agent, aside from its pharmacological actions," study presenter Tiago Mestre, MD, from the Movement Disorders Centre, Toronto Western General Hospital, Ontario, Canada, told Medscape Medical News.

"A different perspective that has never been explored in PD or in neurology is that a patient entering a drug trial with a placebo arm may experience a negative expectation of benefit when facing the concrete possibility of being given placebo, and not the desired new study drug. This deleterious effect of using a placebo has been coined the Lessebo effect," Dr. Mestre said.

Their findings were presented here at the Movement Disorder Society (MDS) 17th International Congress of Parkinson's Disease and Movement Disorders.

The "Lessebo Effect"

To investigate the lessebo effect, Dr. Mestre and colleagues conducted a systematic review of double-blind, randomized, controlled trials of dopamine agonists in PD that used a placebo or active control. They extracted 72 study arms of an active treatment from 39 trials: 30 from trials without a placebo arm (3391 patients with PD) and 42 from trials with a placebo arm (4554 patients with PD).

The researchers calculated the difference between the pooled effect size of the change of the Unified Parkinson's Disease Rating Scale (UPDRS-III) according to the presence or absence of a placebo arm and the probability of placebo assignment.

In support of their hypothesis, preliminary results showed that having a placebo arm does reduce the measured efficacy of an active treatment, with a clinically significant impact. "The measured lessebo effect corresponds to 50% to 80% of what is considered to be a minimally clinical significant change in the motor UPDRS," Dr. Mestre said.

 
The main message for clinicians is that a given antiparkinsonian medication can be associated with an effect of larger magnitude than the one reported in clinical trials. Dr. Tiago Mestre
 

A shorter study duration (12 weeks or less) and early-stage PD were associated with a greater magnitude of the lessebo effect.

"The main message for clinicians is that a given antiparkinsonian medication can be associated with an effect of larger magnitude than the one reported in clinical trials using placebo as control," Dr. Mestre said.

A Very High Bar

"The study points out that clinical trial designs strongly impact results," Christopher Goetz, MD, from Rush University, Chicago, Illinois, who was not involved in the study, said in a conference statement.

"In Europe, comparator trials are much more commonly performed than in North America, so we also may have to consider cultural differences in the study populations in explaining these interesting results," Dr. Goetz said. "If enrolling in a placebo-controlled trial of a new drug actually dampens the impact of the study treatment itself, the bar is very high for demonstrating a clear superiority of the study treatment."

Dr. Mestre cautioned that while this study supports their hypothesis, "it is still exploratory. As such, we are keen to pursue further research on the topic by measuring expectation of benefit in PD patients entering clinical trials and then testing our hypothesis prospectively in a clinical trial. We would also like to see the lessebo effect being explored in other fields of medicine," he told Medscape Medical News.

The study had no funding and the authors have disclosed no relevant financial relationships.

Movement Disorder Society (MDS) 17th International Congress of Parkinson's Disease and Movement Disorders. Abstract 479. Presented Tuesday June 18, 2013.

Comments

3090D553-9492-4563-8681-AD288FA52ACE
Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as:

processing....