When setting out to develop the Placebell©™ method to predict placebo responsiveness in clinical trial patients that considered patient psychology, the Tools4Patient founders realized that they first needed a mechanism to identify and characterize psychological traits related to the placebo response. To do this, the team took advantage of their three greatest resources: their decades of experience as clinical pharmacologists in big pharma; the wealth of literature describing the connection between patient psychology and the placebo response; and existing questionnaires to evaluate patient psychology currently being used for other purposes. From this, the Tools4Patient scientists developed the first iteration of the Multi-Dimensional Psychological Questionnaire (MPsQ) including – but not limited to – questions evaluating specific psychological traits that the scientific literature had suggested were relevant to placebo responsiveness. This questionnaire was then administered to patients in early clinical studies investigating the placebo response in peripheral neuropathic pain. Tools4Patient’s proprietary machine learning-based algorithm then evaluated the relationship between each patient’s psychological features and their placebo response to determine which features were relevant and the relative weights of each feature. With this information, the MPsQ was revised to include only the most pertinent psychological traits.
Currently, the MPsQ questionnaire has been administered to nearly 800 patients in North America, South America, Western Europe, and Australia in clinical trials for multiple types of pain, osteoarthritis, and Parkinson’s disease. The MPsQ has been translated into several languages with full cultural and linguistic validation performed. In early 2020, the MPsQ will be administered in Eastern Europe, and will be included in clinical trials in psychiatric disease and ophthalmology. By the end of 2020, we anticipate that the MPsQ questionnaire will have been administered to nearly 2000 patients.
As part of the validation process, the MPsQ was administered to a subset of N=180 patients repeatedly; some patients even completed the questionnaire multiple times for a period as long as two years after the initial administration. Based on this exercise, Cronbach’s alpha – a measure of tau-equivalent reliability – of the MPsQ is greater than 80%, indicating that this battery is highly repeatable over time. This suggests that the MPsQ measures stable facets of personality, and not emotional status that can vary from day-to-day. The conduct of several trials in pain has also confirmed commonality of individual personality features on the prediction of the placebo response.
The MPsQ data from patients in various geographies has allowed Tools4Patient to begin to understand differences in personality traits related to the placebo response in these geographies. MPsQ data were analyzed across multiple psychological features from N=510 patients in 3 geographies: Western Europe, North American (US and Canada) and Central / South America. This preliminary analysis identified several psychological facets that are consistent across all 3 geographies, as well as some that are different between geographies. While cultural impact on placebo response is a complex phenomenon, these preliminary data as well as other ongoing Tools4Patient developments are contributing to its characterization.
In summary, Tools4Patient has developed a reliable method to characterize and quantify patient personality traits related to the placebo response for inclusion in the Placebell©™ method to predict placebo responsiveness on an individual patient basis. This questionnaire has been widely administered, is stable over time, and has confirmed that some patient psychological traits are consistent in different geographies while others differ between geographies and cultures. When used as part of the Placebell©™ methodology, this tool can reduce variability in clinical trial data related to the placebo response by as much as 30% in various pain indications, with additional validation ongoing in multiple therapeutic areas. Contact us to learn more about the MPsQ questionnaire and the Placebell©™ technology.