Periodic Reporting for period 1 - Psych-STRATA (Psych-STRATA - A Stratified Treatment Algorithm in Psychiatry: A program on stratified pharmacogenomics in severe mental illness)
Reporting period: 2022-10-01 to 2024-03-31
The long-term vision of PSYCH-STRATA is prepare for a shift from usual treatment in Psychiatry towards personalized treatments tailored to the individual patient. This is of immense importance for people with a total lack of response to pharmacological treatment in Schizophrenia (SZ), Bipolar Disorder (BD), and Major depressive Disorder (MDD). The lack of response can have severe consequences for the patients and their environment.
To achieve this overall vision, 6 practical goals have been addressed.
Goal 1: Identification of clinical symptoms and blood-based markers that indicate a total lack of response (called treatment resistance) to drug-based treatment in Schizophrenia (SCZ), bipolar (BP) and Major Depressive Disorder (MDD)
Firstly, we defined comparable definitions for treatment resistance for MDD, BD, SZ, which is a major achievement given the current lack of universal definitions in this field. Secondly, available international datasets according to these definitions were identified and inclusion of these patient groups for DNA analysis is ongoing. Assembling cohorts for genome-wide association analyses (GWAS) in three diagnostic groups is the largest compilation of data ever in this field; hence, novel and previously unseen capacity for genetic analyses on treatment resistance has been built. Thirdly, harmonisation of the relevant clinical phenotypes and genotypic data has been ensured.
Goal 2: Identification of blood-based markers associated with positive treatment outcome
First work has been conducted to identify valid and reproducible markers of treatment outcome in the different patient groups. State-of-the art technologies (the Olink Explore HT panel of 5,000 blood molecules) were identified and confirming the findings are sought using a large publicly available data base (Human Protein Atlas project) is planned.
Goal 3: Randomised Controlled Trials (RCTs) evaluating efficacy and safety of early intensive drug-based treatment
In order to test our findings from the first two goals and to offer patients with identified drug resistance an alternative treatment Goal 3 focused on the design and perform RCTs. In this we will follow the labour-intensive work of obtaining regulatory approval, set up the administrative and logistical structure for the trial, in line with international laws and regulations concerning the conduct of clinical trials as well as recruit the first MDD, BD and SZ participants.
Goal 4: Identification of blood-based markers associated with response to early intense treatment vs normal treatment as evidence-base for a prediction tool
This goal will commence at month 18 and we will start creating a software that will assist to predict treatment response. As we are still identifying the blood-based markers we have still no results in this goal.
Goal 5: Development of a mental health treatment board
Goal 5 is divided into three smaller aims. The first one is to build an artificial intelligence-based tool (using the results of Goal 4) to facilitate the finding of the best possible treatment of patients. The second aim is to develop a mental health board (MHB) consisting of doctors, scientists and patients where individual cases are evaluated for their risk of developing treatment resistance using the said tool, while the third aim is the development of a framework for treatment guidelines using patient-doctor decision-making processes. The innovative MBH will for the first time facilitate early detection and treatment decision-making in severe and at-risk treatment-resistant SZ, BD and MDD patients. Building the MHB includes conceptualizing a framework for a shared decision-making process between patients, physicians and researchers. These findings are currently funnelled into a pilot survey among patients and into three publications on the topics: a) shared decision-making processes; b) patient and physician preference; c) framework of the use of a diagnostic tool in medicine (e.g. for diabetes) from which lessons could be learned. Moreover, novel surveys are prepared to explore attitudes and preferences towards joint decision-making between patients and physicians. Goal 5 team includes a patient representative body that engages in discussion, and co-create surveys, focus groups as well as being represented on the mental health board.
Goal 1: Identification of clinical symptoms and blood-based markers that indicate a total lack of response (called treatment resistance) to drug-based treatment in Schizophrenia (SCZ), bipolar (BP) and Major Depressive Disorder (MDD)
Firstly, we defined comparable definitions for treatment resistance for MDD, BD, SZ, which is a major achievement given the current lack of universal definitions in this field. Secondly, available international datasets according to these definitions were identified and inclusion of these patient groups for DNA analysis is ongoing. Assembling cohorts for genome-wide association analyses (GWAS) in three diagnostic groups is the largest compilation of data ever in this field; hence, novel and previously unseen capacity for genetic analyses on treatment resistance has been built. Thirdly, harmonisation of the relevant clinical phenotypes and genotypic data has been ensured.
Goal 2: Identification of blood-based markers associated with positive treatment outcome
First work has been conducted to identify valid and reproducible markers of treatment outcome in the different patient groups. State-of-the art technologies (the Olink Explore HT panel of 5,000 blood molecules) were identified and confirming the findings are sought using a large publicly available data base (Human Protein Atlas project) is planned.
Goal 3: Randomised Controlled Trials (RCTs) evaluating efficacy and safety of early intensive drug-based treatment
In order to test our findings from the first two goals and to offer patients with identified drug resistance an alternative treatment Goal 3 focused on the design and perform RCTs. In this we will follow the labour-intensive work of obtaining regulatory approval, set up the administrative and logistical structure for the trial, in line with international laws and regulations concerning the conduct of clinical trials as well as recruit the first MDD, BD and SZ participants.
Goal 4: Identification of blood-based markers associated with response to early intense treatment vs normal treatment as evidence-base for a prediction tool
This goal will commence at month 18 and we will start creating a software that will assist to predict treatment response. As we are still identifying the blood-based markers we have still no results in this goal.
Goal 5: Development of a mental health treatment board
Goal 5 is divided into three smaller aims. The first one is to build an artificial intelligence-based tool (using the results of Goal 4) to facilitate the finding of the best possible treatment of patients. The second aim is to develop a mental health board (MHB) consisting of doctors, scientists and patients where individual cases are evaluated for their risk of developing treatment resistance using the said tool, while the third aim is the development of a framework for treatment guidelines using patient-doctor decision-making processes. The innovative MBH will for the first time facilitate early detection and treatment decision-making in severe and at-risk treatment-resistant SZ, BD and MDD patients. Building the MHB includes conceptualizing a framework for a shared decision-making process between patients, physicians and researchers. These findings are currently funnelled into a pilot survey among patients and into three publications on the topics: a) shared decision-making processes; b) patient and physician preference; c) framework of the use of a diagnostic tool in medicine (e.g. for diabetes) from which lessons could be learned. Moreover, novel surveys are prepared to explore attitudes and preferences towards joint decision-making between patients and physicians. Goal 5 team includes a patient representative body that engages in discussion, and co-create surveys, focus groups as well as being represented on the mental health board.
The major achievements beyond the state-of-the art so far are:
- creating a unified definition of total lack of treatment response in the three patient groups.
- the unique set of blood-based markers in psychiatric research will create reference data and can serve as platform for other research topics within Psychiatry.
- new technologies beyond the state of the art such as stem-cell research will help to validate the blood-based marker findings.
- a pharmacological treatment will be tested in drug-resistant patients that are commonly used in chronic stages of the illness in earlier, non-chronic stages of the illness (clinical trial design).
- the development of a mental health board (MHB) is beyond current practise in Psychiatry.
- creating a unified definition of total lack of treatment response in the three patient groups.
- the unique set of blood-based markers in psychiatric research will create reference data and can serve as platform for other research topics within Psychiatry.
- new technologies beyond the state of the art such as stem-cell research will help to validate the blood-based marker findings.
- a pharmacological treatment will be tested in drug-resistant patients that are commonly used in chronic stages of the illness in earlier, non-chronic stages of the illness (clinical trial design).
- the development of a mental health board (MHB) is beyond current practise in Psychiatry.