NEW YORK – A new European project aims to combine real-world electronic health records with genomic data from biorepositories and clinical trial data to develop new tools to help guide treatment selection for patients with severe mental disorders.
Researchers from the University of Oslo are leading the effort, called Realment, along with a consortium of 13 partners. The project has a budget of €6 million ($7.3 million) and will commence on June 1 with an end date of May 31, 2025. Investigators hope to deploy a clinical management platform to enable clinicians to optimize patient therapies.
"In psychiatry, most antipsychotic drugs have the same effect," noted Ole Andreassen, a professor in the University of Oslo's Institute of Clinical Medicine. "Selection of drugs is therefore based on adverse effect profiles. The response rate is about 60 to 70 percent and it is difficult to predict the response in a given individual." It therefore takes time, sometimes years, to determine whether or not a therapy is working.
"It's a lot of trial and error," said Andreassen. "It's not like measuring blood or blood pressure; it's based on an assessment of behavioral symptoms." The idea behind Realment is to survey data amassed in national health registries, in biobanks, and from clinical trials to develop tools that can tell clinicians how a mental health patient might respond to a given therapy.
"If you can avoid side effects, you can help patients and families and save time and money currently wasted on nonfunctioning treatments," said Andreassen.
Some companies and institutions taking part in Realment include Karolinska Institute, the Capital Region of Denmark, the University of Helsinki, the University of Tartu in Estonia, DeCode Genetics, Cardiff University in the UK, VU Amsterdam, and the University of Bari Aldo Moro in Italy. Others are DNV, a Norwegian quality assessment company; CoreTechs Labs, a US imaging company; Smerud Medical Research, an Oslo-based CRO; the European College of Neuropsychopharmacology; and Janssen Pharmaceuticals, which is headquartered in Beerse, Belgium.
Andreassen underscored that the concept of Realment is not to generate new data but rather take advantage of existing data holdings, particularly in the Northern European countries taking part in the effort. "The basic driver is the Nordic biobanks, health registries, and hospital records in Scandinavia, Finland, Estonia, and Iceland," said Andreassen. Other groups are focused on medical record data collection and clinical research, as well as the development of analytical tools that can later be commercialized. J&J and DeCode, in particular, have extensive information related to mental illness, he said, and the Nordic health registries have data on treatment outcome.
"We will collect real-world data on treatment and do a large population study," said Andreassen.
Altogether, the Realment data set should include randomized clinical trial data on 10,000 subjects and whole-genome genotyping data from roughly 1.9 million people, contributed by DeCode, the Estonian Biobank at the University of Tartu, and other Realment participants. The data assessed will mainly be whole-genome array data, Andreassen noted. "It's a different ballgame with sequencing data because that is another level of complexity and much smaller samples are sequenced," he said. Still, Realment includes some targeted pharmacogenetics projects based on sequencing data. "Some of the variance in response and adverse effects of psychopharmacological agents can be due to rare variants," says Andreassen.
Lili Milani, professor in pharmacogenetics at the Estonian Genome Center at the University of Tartu, noted that their experience with a population-specific reference panel of 3,000 sequenced genomes has been "excellent for imputation of common and rare variants" in the 200,000 genotyped participants of the Estonian Biobank.
"We recently found a novel genetic association with penicillin allergy extracted from electronic health records, and we are eager to look into the genetics of treatment outcomes in psychiatric disorders using similar real-world data and methods for simulated clinical trials," Milani said.
Andreassen pointed out that many Realment participants have been partners on other projects and have learned to cooperate to support large-scale genetics. One such project is CoMorMent, a €6 million EU-funded project that aims to investigate the genetic link between cardiovascular disease and mental disorders.
"It's really an illustration of the big opportunities there are if the Nordic region comes together," said Andreassen. "There are so many opportunities here." Part of taking advantage of that opportunity is harmonizing and standardizing data across resources, so that it can be analyzed for a given research question. Though most of the data cannot leave the countries, the scientists can align their data repositories. "We use a distributed analysis system," Andreassen commented. "That way we can share tools to calculate and bring together the power of all of the different samples."
All that data will be used to power machine-learning tools that might predict optimal therapies for patients. By the time the project wraps up in 2025, the Realment team hopes to integrate the new tools in a clinical management platform.
"I think we will have much better knowledge about which factors are associated with different treatment outcomes in patients with mental illness," predicts Andreassen. "I think we will also manage to take some of those into clinically useful prediction and stratification tools for specific clinical use cases, so that the physician or psychiatrist will be able to select the best drug for a patient in need for new medication without a trial-and-error phase," he said.
Andreassen said that Realment is different from previous clinical trials of antipsychotic drugs in that it will include data on patients covering, in some cases, decades. Denmark's health registry, for instance, has data on patients going back to 1968. "Clinical trials can last a few weeks or months, but there are few long-term studies that have been done," he said. "That is indeed something we can look into here, as many patients receive medication for years."