ISCTM 2009 Autumn Conference – Placebo Response Workshop Summary

Summary of Placebo Response in CNS Clinical Trials Workshop at the ISCTM 2009 Autumn Conference in San Diego

The purpose of the workshop was to gather experts to review the evidence regarding placebo response in psychiatry trials and brainstorm ways to manage this phenomenon and make some recommendations. The workshop was attended by over 75 participants.

Co-Chairs: Amir Kalali and Charles Bowden

Speakers:
Craig Mallinckrodt
Amir Kalali
Charles Bowden
Jelena Kunovac

There were four speakers representing different sectors of professionals involved in clinical trials, but the majority of the time was spent in discussion of the topic.

It was decided to focus on and discuss three main categories of factors impacting placebo response:

•    Study Design
•    Site characteristics
•    Subject characteristics

Study Design

•    Study designs must have “Simplicity to Fit Purpose” e.g appropriate outcome measures and not “overburdening” protocols and subjects. This may also have direct impact on types of patients willing to enter clinical trials
•    Treatment allocation – utilize strategies that randomize more patients to PBO
•    Use of variable PBO lead-in  may be helpful
•     Patient rated outcomes may be helpful in non-psychotic disorders  reducing recall and rater bias
•    Use of MMRM analysis and subscales  have shown better signal detection
•    Adding threshold scores for several key symptoms not easily distorted may help increase signal detection.  These can include observed symptoms, as opposed to purely reported symptoms
•    Different strategies for validating baseline severity such as patient ratings, and independent assessment should be explored

Site  Characteristics

•    Importance of site culture
•    Principal Investigator  involvement
•    Access to appropriate patients
•    Careful selection of appropriate patients
•    Site personnel experience, expertise and conscientiousness
•    Communication to patients and nature of interactions
•    Strive for evidence based site selection by sponsors

Subject Characteristics

•    Subject characteristics shown to impact signal detection
•    True baseline severity/acuity
•    Issues with subjects who have participated in many clinical trials and possible “professional” subjects
•    Subject motivation for participating
•    Subject expectations of improvement
•    Subject understanding of their role as a research participant versus clinical care

Recommendations

•    Study designs must have “Simplicity to Fit Purpose”
•    More intense sponsor engagement with sites
•    Sponsors need to share data with sites with regards to signal detection to facilitate improvement
•    Develop systems of “flagging” inappropriate patients

Prepared by Workshop Co-chairs: Amir Kalali, MD; Charles Bowden, MD