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Principal Investigator: Sebastian G. Schneeweiss
Organization: BRIGHAM AND WOMEN'S HOSPITAL
Fiscal Year: 2024
Award: $636,546
Funding agency: National Institute of Arthritis and Musculoskeletal and Skin Diseases
Summary:
Severe treatment recalcitrant atopic dermatitis (AD) is a debilitating condition with substantial population
impact. Dermatology has experienced the emergence of targeted immuno-modulating drugs (IMDs) that have
unprecedented efficacy in treating AD. Their optimal use is still unknown because their safety remains
insufficiently characterized.
A range of serious side effects are conceivable based on the immunologic pathways although it is unlikely that
they will all play out in clinical practice. Quantifying or refuting these adverse effects is critical for a clinical
benefit-risk assessment and personalized treatment decisions. Existing trials have not answered these
questions and are unlikely to address them in the near future. The resulting uncertainty has led to both overly
restrictive but also aggressive prescribing of highly efficacious IMDs and this proposal aims to close this glaring
knowledge gap.
We propose a population-based prospective drug safety monitoring system leveraging existing data sources
that shortens the time to insights and provides high validity findings through advanced causal inference
methods. Analyses of longitudinal healthcare databases cover a source population of >78 million Americans
and include commercially insured and Medicaid beneficiaries. New and urgently needed safety insights will
reflect clinical practice, including populations typically excluded from RCTs, like children, women in
reproductive age, patients with complex diseases, minority populations, and patients with existing risk factors.
The size of the claims data source increases statistical power and the linkage to electronic health records in
subsets improves clinical depth. We use causal inference methods that demonstrated high validity in pilot data
and complement them with a novel data mining approach to identify unsuspected events. Analyses are done
with highest transparency and reproducibility to support clinical decision making. This project’s finding on the
optimal use of IMDs in clinical practice will lead to more targeted prescribing and benefit large patient groups,
including populations underrepresented in RCTs: children, older adults, pregnant women, racial minorities,
patients with pre-existing infections, cancers, VTE and others.
This project is highly innovative as it will generate directly applicable clinical insights on the safe and targeted
use of new immuno-modulating drugs (IMDs) to treat atopic dermatitis. Leveraging existing claims data
sources with added EHR data it builds on novel methods for causal inference to mitigate biases arising in real-
world data analyses in dermatology. The expedited evidence generation via the proposed prospective
monitoring system combined with our track record in pharmacoepidemiologic analyses, this research will
efficiently close knowledge gaps for optimal IMD use in many underrepresented and high-risk patients.
Terms: <0-11 years old><Active Follow-up><Address><Adverse effects><Age><Algorithms><American><Atopic Dermatitis><Atopic Eczema><Atopic Neurodermatitis><Bacterial Infections><COVID-19><CV-19><Calibration><Cancers><Cell Communication and Signaling><Cell Signaling><Cellular Immune Function><Child><Child Youth><Children (0-21)><Clinical><Complement><Complement Proteins><Complex><Coronavirus Infectious Disease 2019><Cutaneous Disorder><Data><Data Analyses><Data Analysis><Data Bases><Data Sources><Databases><Dermatologist><Dermatology><Dermatoses><Development><Disease><Disorder><Disseminated Neurodermatitis><Drug usage><Drugs><Electronic Health Record><Ethnic Origin><Ethnicity><Event><Exclusion><Exposure to><Future><Generations><Health><Healthcare><IMiD><Immune><Immune modulatory therapeutic><Immunes><Immunochemical Immunologic><Immunologic><Immunological><Immunologically><Immunologics><Immunosuppression><Immunosuppression Effect><Immunosuppressive Effect><Individuals from minority><Individuals of minority><Infection><Intracellular Communication and Signaling><Investigation><Knowledge><Link><Malignant Neoplasms><Malignant Tumor><Marketing><Medicaid><Medication><Methods><Minority Female><Minority Groups><Minority People><Minority Population><Minority Women><Minority individual><Modernization><Modification><Monitor><Morbidity><Morbidity - disease rate><NIAMS><National Institute of Arthritis, and Musculoskeletal, and Skin Diseases><Opportunistic Infections><Outcome><Pathway interactions><Patient outcome><Patient-Centered Outcomes><Patient-Focused Outcomes><Patients><Pattern><Pharmaceutical Epidemiology><Pharmaceutical Preparations><Pharmacoepidemiology><Placebos><Play><Population><Predisposition><Pregnant Women><Production><QOL><Quality of life><Race><Races><Reproducibility><Research><Residual><Residual state><Risk><Risk Factors><Risk-Benefit Assessment><Safety><Scanning><Seasons><Sham Treatment><Signal Transduction><Signal Transduction Systems><Signaling><Skin Diseases><Skin Diseases and Manifestations><Source><Subgroup><Susceptibility><System><Testing><Time><Uncertainty><Underrepresented Ethnic Minority><Underrepresented Groups><Underrepresented Minority><Underrepresented Populations><Update><Variant><Variation><Venous><Viral Diseases><Virus Diseases><Woman><active followup><ages><allergic dermatitis><allergic eczema><analyzing longitudinal><bacteria infection><bacterial disease><bear children><bearing children><beneficiary><biological signal transduction><child bearing><childbearing><chronic inflammatory skin><clinical applicability><clinical application><clinical decision support><clinical decision-making><clinical practice><co-morbid><co-morbidity><cohort><comorbidity><comparative safety><complementation><coronavirus disease 2019><coronavirus disease-19><coronavirus infectious disease-19><cutaneous disease><cytokine><data base><data interpretation><data mining><datamining><dermal disease><dermal disorder><design><designing><developmental><doubt><drug epidemiology><drug market><drug safety><drug use><drug/agent><economic indicator><electronic health care record><electronic health medical record><electronic health plan record><electronic health registry><electronic medical health record><expectant mother><expecting mother><experience><flu><follow up><follow-up><followed up><followup><health care><high risk><immune function><immune modulating agents><immune modulating drug><immune modulating therapeutics><immune modulatory agents><immune modulatory drugs><immune suppression><immune suppressive activity><immune suppressive function><immunomodulating agents><immunomodulating drugs><immunomodulator agent><immunomodulator drug><immunomodulator medication><immunomodulator prodrug><immunomodulator therapeutic><immunomodulatory agents><immunomodulatory drugs><immunomodulatory therapeutics><immunosuppressive activity><immunosuppressive function><immunosuppressive response><improved><infection risk><inhibitor><innovate><innovation><innovative><insight><kids><longitudinal analysis><malignancy><medication safety><neoplasm/cancer><new approaches><novel><novel approaches><novel strategies><novel strategy><off-label application><off-label prescribing><off-label use><older adult><older adulthood><pathway><patient oriented outcomes><personalization of treatment><personalized medicine><personalized therapy><personalized treatment><pharmaceutical safety><pharmacoepidemiologic><pharmacoepidemiological><placebo control trial><placebo controlled trial><population based><pregnant mothers><prior authorization><prospective><racial><racial background><racial minority><racial origin><real time monitoring><realtime monitoring><reproductive><sham therapy><side effect><skin disorder><socio-economic><socio-economically><socioeconomically><socioeconomics><standard care><standard treatment><targeted drug therapy><targeted drug treatments><targeted therapeutic><targeted therapeutic agents><targeted therapy><targeted treatment><treatment choice><trend><under representation of groups><under represented groups><under represented people><under represented populations><under-representation of minorities><under-represented minority><underrepresentation of groups><underrepresentation of minorities><underrepresented people><venous thromboembolism><viral epidemic><viral infection><virus infection><virus-induced disease><young woman><youngster>