Description

The placebo effect, the nonspecific response to treatment not associated with active treatment, has a longstanding tradition in research with multiple systematic reviews and meta-analyses demonstrating the effects of placebo in areas as divergent as cardiovascular disease (Sheldon & Opie-Moran, 2017), depression (Meister et al 2017), and irritable bowel syndrome (Flik et al 2017). Less commonly studied is the "nocebo" effect _ the reporting of side effects that are not specific to the active treatment. While variably defined, depending on the context, a reasonable definition would be that they generally are "psychobiological events attributable to the overall therapeutic context...[the] placebo effect would be the benefits provoked by an inert substance, and the nocebo effect is the induction of true or perceived harm after treatment with an inactive substance." (Chavarria et al 2017). It has become clear that there are both psychological/neurobiological reasons for these effects. The paradigms in which the placebo response has most frequently been studied have included the study of pain (Benedetti et al 2003) and, most recently, CNS studies including depression (Kirsch et al 2014).

The placebo response is highly individual, yet there are some commonly known associations with individual propensity towards demonstrating the placebo response, including certain genetic polymorphisms and neurobiological markers of frontal lobe functioning. While these can be taken into account when attempting to either maximize or minimize the placebo response, a more common approach is to maximize or minimize the response experimentally _ that is to say that there are techniques within a study which can allow for the possibility of wider separation of active medication from placebo (minimizing the placebo response) or to increase the likelihood of placebo responses (maximizing the placebo response). The latter is particularly helpful in situations where the clinician would like to enhance the treatment by harnessing the additional power of the placebo. This has been shown to be useful in analgesia and in depression. Most of the effects come from carefully managing the expectations of the patient towards positive response. Because much of the placebo response appears to be based on motivation or conditioning, the clinician can manipulate these factors to encourage the patient to feel a higher level of response. Note that this does not mean that there needs to be deception involved, in that even patients who know they are receiving a placebo, when properly motivated and encouraged, can note an enhanced response.

In clinical trials, the goal is most typically to reduce the placebo and the nocebo responses, or to enhance the differences between active drug and placebo. Here, again, there are experimental design methods that can be used to create a research environment that will diminish placebo and nocebo responses. These techniques include careful selection of patients and outcome measures, avoiding enrichment or multidosing studies, and careful use of run-in and withdrawal designs.

Important questions about managing the placebo response remain. This meeting will address the following issues:

  • Update on the placebo problem in pharmaceutical trials
  • The effects of the placebo response in pain and CNS trials
  • Adjusting trial designs to enhance or reduce the placebo response
  • How to develop a comprehensive strategy to manage the placebo response

The presentations will incorporate multiple perspectives, including the perspectives of researchers, clinicians, patients, and industry. Participants will be expected to gain insight into the placebo problem and how it can affect their reading of the research literature and their approach to patients.

Learning Objectives

After this program, participants will be able to:

  • Define the placebo response
  • Summarize the research context of the placebo response and its effects in clinical trials
  • Describe the types of scientific studies and methodologies used to study the placebo response
  • Identify the process for utilizing the placebo response to the advantage of treatment
  • Discuss critical methodologies in clinical trials to control for the placebo response
  • Describe a comprehensive approach to managing the placebo response

Agenda

Content and faculty subject to change.

FRIDAY, JUNE 8, 2018

8:00-8:15 am

Welcome and Introductions
Maurizio Fava, MD

The "Issues" with Placebos

8:15-9:00 am

Historical Overview of The Placebo Problem in CNS Drug Trials
Stephen Peroutka, MD, PhD

9:00-9:45 AM

Placebo in Pain Trials
Nat Katz, MD

9:45-10:00 AM

Coffee Break

10:00-10:45 AM

The Rise of Placebo Responses in Alzheimer's Disease and Epilepsy
Steve Arnold, MD

10:45-11:30 AM

Enhancing the Placebo Response
Ted Kaptchuk, MD

11:30-12:00 PM

Discussions and Questions for the Speakers
Moderator: Maurizio Fava, MD

12:00-1:00 pm

Lunch

Placebo "Solutions"

1:00-1:45 PM

Critical Methodological and Design Decisions in CNS Trials
Maurizio Fava, MD

1:45-2:30 PM

Subject and Rater Quality Assurance
Ottavio Vitolo, MD

2:30-3:15 PM

Manipulating Expectations in Psychiatric Drug Trials
George I. Papakostas, MD

3:15-4:00 PM

Discussions and Questions for the Speakers
Moderator: Maurizio Fava, MD

4:00 pm

Adjourn

Faculty

  • Translational Neurology Head
    Interdisciplinary Brain Center
    Massachusetts General Hospital

    Professor of Neurology
    Harvard Medical School
  • Director, Division of Clinical Research of the MGH Research Institute
    Executive Vice Chair, Department of Psychiatry
    Executive Director, Clinical Trials Network & Institute (CTNI)
    Massachusetts General Hospital

    Associate Dean for Clinical & Translational Research
    Slater Family Professor of Psychiatry
    Harvard Medical School
  • Professor of Medicine
    Professor of Global Health and Social Medicine
    Harvard Medical School

    Director
    Program in Placebo Studies & Therapeutic Encounter
    Beth Israel Deaconess Medical Center
  • Adjunct Associate Professor of Anesthesia
    Tufts University School of Medicine

    CEO
    Analgesic Solutions
  • Scientific Director, Clinical Trials Network & Institute (CTNI)
    Massachusetts General Hospital
    Associate Professor of Psychiatry
    Harvard Medical School
  • Neuropsychiatry Fellow, Department of Psychology, MGH
    Research Fellow, Depression Clinical and Research Program, MGH
    Instructor in Psychiatry, Harvard Medical School

Target Audience

This live meeting is intended for:

  • Academic Clinical Researchers
  • FDA staff

Accomodations

We have secured rooms at the Fairmont Copley Plaza, Boston.

Please specifiy that you are attending the MGH Placebo conference when you call.

Rate: $389/night plus tax

Phone: 617-267-5300

Address: 138 St. James Avenue, Boston, MA 02116

Location

Fairmont Copley Plaza, 138 Saint James Avenue, Boston, Massachusetts, United States