CAUSALab
CAUSALab generates, repurposes and analyzes health data so that key decision makers – regulators, clinicians, policy makers and you – can make more informed decisions.
What We Do
CAUSALab has helped develop language and methodologies that are now standard for researchers around the world. Our work keeps pushing boundaries and innovating on the cutting-edge of causal inference methods. Our investigator team includes global experts in target trial emulation, g-methods and AI, transportability and benchmarking & others. We develop and implement these methods using real world data from electronic health records, administrative claims, biobanks, national registers, disease registries and randomized trials.
Our applied research focuses on implementing the frameworks to determine comparative effectiveness and safety of health and policy interventions. Our areas of work include infectious diseases, cardiovascular diseases, cancer, mental health & pregnancy.
CANCER-CAUSAL implements state-of-the-art causal inference methods to support cancer research.
Many important decisions about cancer control – including how to best prevent, detect, and treat cancer – must be made in the absence of evidence from randomized trials, which are often impractical or too lengthy to provide a timely answer. In these cases, we combine large health databases and sound causal inference methodology to provide the best available evidence to inform health decision-making and future trial design.
Our research program implements a systematic approach to cancer comparative effectiveness and safety research, leveraging traditional epidemiologic cohorts and novel platforms of electronic health records.
For example, in the first application of the parametric g-formula to prostate cancer research, we leveraged high-quality cohort data to provide the first survival estimates of adhering to various physical activity strategies that are sustained over time, including those recommended by current guidelines, after diagnosis with cancer.
- Dickerman BA, Giovannucci E, Pernar CH, Mucci LA, Hernán MA. Guideline- based physical activity and survival among U.S. men with nonmetastatic prostate cancer. American Journal of Epidemiology. 2019; 188(3): 579-586. PMCID: PMC6395165
In addition, we developed a causal inference framework to emulate target trials of cancer outcomes in a nationwide database of electronic health records linked to registries in the U.K. Our research demonstrated that previous randomized-observational discrepancies for statins and cancer appear to be due to the analytic approach and not any inherent problems in the observational data, and that these discrepancies disappear when observational data are analyzed using methods consistent with the causal inference framework.
- Dickerman BA, García-Albéniz X, Logan RW, Denaxas S, Hernán MA. Avoidable flaws in observational analyses: an application to statins and cancer. Nature Medicine. 2019; 25: 1601-1606. PMCID: PMC7076561
We have extended this causal inference framework to different cancer-causal questions, study designs, and data sources.
- Dickerman BA, García-Albéniz X, Logan RW, Denaxas S, Hernán MA. Emulating a target trial in case-control designs: an application to statins and colorectal cancer. International Journal of Epidemiology. 2020; 49(5): 1637-1646. PMCID: PMC7746409
- Dickerman BA, García-Albéniz X, Logan RW, Denaxas S, Hernán MA. Evaluating metformin strategies for cancer prevention: a target trial emulation using electronic health records. Epidemiology. 2023;34(5):690-9. PMCID: PMC10524586
- Guo F, McGee EE, Chiu Y, Giovannucci E, Mucci LA, Dickerman BA. Evaluating recommendation-based dietary and physical activity strategies for prostate cancer prevention: a target trial emulation in the Health Professionals Follow-up Study. American Journal of Epidemiology. 2024. Epub.
- García-Albéniz X, Hsu J, Etzioni R, Chan JM, Shi J, Dickerman BA, Hernán MA. PSA screening and prostate cancer mortality: an emulation of target trials in U.S. Medicare. JCO Clinical Cancer Informatics. 2024. In press.
Lastly, our work extends to the conduct and analysis of randomized trials, including the Nordic-European Initiative on Colorectal Cancer (NordICC) trial – a population-based trial which provided the first randomized evidence on colonoscopy screening to prevent colorectal cancer and related death. Our estimates of colonoscopy screening effectiveness and efficacy provided key evidence for priority setting on cancer screening interventions.
- Bretthauer M, Løberg M, Wieszczy P, Kalager M, Emilsson L, Garborg K, Rupinski M, Dekker E, Spaander M, Bugajski M, Holme Ø. Zauber AG, Pilonis ND, Mroz A, Kuipers EJ, Shi J, Hernán MA, Adami HO, Regula J, Hoff G, Kaminski MF. Effect of colonoscopy screening on risks of colorectal cancer and related death. New England Journal of Medicine. 2022;387(17):1547-56.
Ongoing CANCER-CAUSAL Projects include:
Prevention (Primary, Tertiary) of Cancer
- Methodological challenges in estimating the long-term effects of lifestyle interventions for cancer survivors
- Guideline-based physical activity and quality of life among men with nonmetastatic prostate cancer: a target trial emulation in the Health Professionals Follow-up Study
Early Detection of Cancer
- Effect of colonoscopy screening on risks of colorectal cancer and related death: instrumental variable estimation of per-protocol effects
- Prostate-specific antigen-based screening strategies and prostate cancer mortality: a target trial emulation using electronic health records
- Identifying smarter screening strategies for prostate cancer
Treatment of Cancer
- Statin therapy for the prevention of lethal outcomes among men diagnosed with nonmetastatic prostate cancer: a target trial emulation using electronic health records
- Adjuvant bone-modifying agents and mortality among older postmenopausal women with early-stage breast cancer
- Evaluating different sequences, timing, and combinations of cancer treatments
Surveillance of Cancer
- Comparative effectiveness of cystoscopy surveillance strategies on mortality in non-muscle invasive bladder cancer: a target trial emulation using real-world data
Funding:
CANCER-CAUSAL is funded by the U.S. National Cancer Institute (R00 CA248335; PI: Dickerman).
Contact:
Barbra Dickerman
Hep-CAUSAL is a consortium of cohorts of people with HIV and HCV co-infection in Europe and North America. The research team includes investigators from each of the participating studies and from the coordinating center.
HIV and HCV co-infection places patients at risk of morbidity and mortality from hepatic disease (cirrhosis, hepatocellular carcinoma) and extra-hepatic morbidities (cardiovascular disease, kidney disease, diabetes). Treatment with direct-acting antiviral agents (DAA) cures HCV infection in about 95% of patients. However, even after HCV cure is achieved, hepatic and extra-hepatic disease remains risks, and some individuals become reinfected with HCV.
By combining observational data and cutting-edge causal inference methods, HepCAUSAL estimates the long-term risk of HCV reinfection, hepatic disease, and extra-hepatic disease under current guidelines that recommend DAA treatment for all persons with HIV and HCV co-infection. As millions of people are expected to receive DAA treatment in the US and globally, our findings inform clinical guidelines and optimal screening strategies and how to maximize the benefits of DAA treatment in the long-term.
Participating Cohorts:
- Austrian HIV Cohort Study (AHIVCOS; Austria)
- Athens Multicenter AIDS Cohort Study (AMACS; Greece)
- ANRS CO3 Aquitaine Cohort (Aquitaine; France)
- Stichting HIV Monitoring / AIDS Therapy Evaluation in the Netherlands study (ATHENA; Netherlands)
- Boston Medical Center (BMC; USA)
- Canadian Co-Infection Cohort (CCC; Canada)
- Spanish HIV Research Network (CoRIS; Spain) cohort
- ANRS CO13 HEPAVIH cohort (France)
- Italian Cohort of Antiretroviral-Naïve Patients (ICONA; Italy)
- Catalano Balear HIV population cohort (PISCIS; Spain)
- South Alberta Clinic cohort (SAC; Canada)
- Swiss HIV Cohort Study (SHCS; Switzerland)
- Veterans Aging Cohort Study (VACS; USA)
Funding:
Our research is supported by the U.S. National Institute of Allergy and Infectious Diseases (R37 AI102634; PI: Hernán) and the Providence/Boston Center for AIDS Research (P30AI042853).
Contact:
Sara Lodi
The HIV-CAUSAL Collaboration is a multinational consortia of follow-up studies of persons with HIV in Europe and North America. The research team includes investigators from each of the participating studies and from the coordinating center. HIV-CAUSAL investigators love randomized trials but know that trials cannot answer all important questions for HIV clinical management in a timely manner. This is why they also use data from observational cohorts to conduct research that improves the lives of people who HIV.
For about two decades, the HIV-CAUSAL Collaboration has been at the forefront of development and implementation of methods to compare the effectiveness of clinical strategies using observational cohorts. The methodological work pioneered by the Collaboration has transformed HIV cohort analysis in the 21st century.
Besides being an incubator for new methodologies, the HIV-CAUSAL Collaboration conducts clinical research designed to inform evidence-based guidelines and the planning of randomized trials. Findings from the HIV-CAUSAL Collaboration played a prominent role in the now largely settled discussions about when to start antiretroviral therapy. Our recent research has contributed to a better understanding of the effects of antiretroviral therapy on opportunistic infections, neurological conditions, and viral resistance, as well to the study of dynamic strategies for the treatment and monitoring of individuals living with HIV.
In addition, the Collaboration facilitates understanding and training in causal modeling across leading HIV observational research groups.
Participating Cohorts:
- Austrian HIV Cohort Study (AHIVCOS; Austria)
- Athens Multicenter AIDS Cohort Study (AMACS; Greece)
- ANRS CO3 Aquitaine Cohort (Aquitaine; France)
- Stichting HIV Monitoring / AIDS Therapy Evaluation in the Netherlands study (ATHENA; Netherlands)
- Boston Medical Center (BMC; USA)
- Canadian Co-Infection Cohort (CCC; Canada)
- UK Collaborative HIV Cohort Study (UK CHIC)
- Spanish HIV Research Network (CoRIS; Spain) cohort
- French hospital database on HIV (FHDH; France)
- ANRS CO13 HEPAVIH cohort (France)
- Italian Cohort of Antiretroviral-Naïve Patients (ICONA; Italy)
- Catalano Balear HIV population cohort (PISCIS; Spain)
- Primary Infection cohort (PRIMO; France)
- Seroconverters and primary infection cohort (SEROPRI; France)
- South Alberta Clinic cohort (SAC; Canada)
- Swiss HIV Cohort Study (SHCS; Switzerland)
- Veterans Aging Cohort Study (VACS; USA)
- Mass General Brigham HIV cohort (USA)
Funding:
Our research is supported by the U.S. National Institute of Allergy and Infectious Diseases (R37 AI102634; PI: Hernán).
Contact:
Miguel Hernán
CAUSALab is the Methods Core of the Laboratory for Early Psychosis (LEAP) Center, one of the U.S. National Institute of Mental Health’s Advanced Laboratories for Accelerating the Reach and Impact of Treatments for Youth and Adults With Mental Illness (ALACRITY) Research Centers.
The FEP-CAUSAL Collaboration is an international consortium of prospective cohorts of individuals with first episode psychosis (FEP) that is coordinated by LEAP’s Methods Core. The research team includes investigators from each of the participating studies and from the coordinating center.
The goal of FEP-CAUSAL is to study interventions that can guide treatment choices of clinicians and patients with first episode of psychosis in the absence of randomized trials. The clinical research produced by FEP-CAUSAL investigator is meant to inform evidence-based guidelines and the planning of randomized trials.
- Szmulewicz AG, Martínez-Alés G, Logan R, Ferrara M, Kelly C, Fredrikson D, Gago J, Conderino S, Díaz-Caneja CM, Galvañ J, Thorpe L, Srihari V, Yatham L, Sarpal DK, Shinn AK, Arango C, Öngür D, Hernán MA. Antipsychotic drugs in first-episode psychosis: a target trial emulation in the FEP-CAUSAL Collaboration. Am J Epidemiol. 2024 Aug 5;193(8):1081-1087.
- Szmulewicz AG, Martínez-Alés G, Logan R, Ferrara M, Kelly C, Fredrikson D, Gago J, Conderino S, Díaz-Caneja CM, Galvañ J, Thorpe L, Srihari V, Yatham L, Sarpal DK, Shinn AK, Arango C, Öngür D, Hernán MA. Comparative effectiveness of long-acting injectable vs. oral antipsychotic medication after a first episode of psychosis. Nature Mental Health, 2025. Accepted, In Press.
Funding:
Our research is supported by the U.S. National Institute of Mental Health (grant P50 MH115846 (PIs: Öngür, Hsu, Hernán) and by the Brain & Behavior Research Foundation (Grant 2022-31313; PI: Szmulewicz).
Contact:
Alejandro Szmulewicz MD PhD (aszmulewicz@hsph.harvard.edu)
CAUSALab investigators have pioneered the application of the target trial framework to the generation of evidence on the safety and effectiveness of interventions during pregnancy. CAUSALab works in partnership with H4P, The Harvard Program on Perinatal and Pediatric Pharmacoepidmiology, which includes investigators from Brigham and Women’s Hospital, Harvard Medical School, and the Harvard T.H. Chan School of Public Health, learn more about the team.
The H4P team works to fill the gap of information on the effects of drugs and vaccines on the mother and the developing fetus. Through this work, they are determined to improve clinical decisions and improve health outcomes for this historically underserved population. Learn more about their research.
Funding:
Our research is supported by grant R01 HD097778 (PI: Hernández-Díaz) from the National Institute of Child Health and Human Development, U.S. National Institutes of Health.
Contact:
Sonia Hernández-Díaz
Come back soon for more information about research on benchmarking and transportability.
Best wishes to VA CAUSAL!
In 2019, investigators from the VA and Harvard’s CAUSALab launched the VA CAUSAL enterprise. The goal of this unique partnership was to provide VA investigators with expertise in the application of causal inference methodology to the rich databases of the Veterans Administration. Together, we took on challenging projects for the prevention of suicide, dementia, cancer, infectious diseases, and other health problems in U.S. veterans. We also developed methodological resources and code for target trial emulation and made it available to all VA investigators.
When the funding landscape shifted in 2025, VA and CAUSALab jointly supported the partnership. CAUSALab contributed its own resources, reflecting its commitment to sustain research aimed at improving veterans’ health.
In 2026, we were proud to hear that the VA Cooperative Studies Program, with its causal inference capability now established, will carry forward VA CAUSAL operations independently. At CAUSALab, we are honored to have played a part in that achievement and delighted to see VA CAUSAL take flight.
For an overview of VA CAUSAL activities, watch the 2025 Kolokotrones Symposium “Building a Learning Health System: the VA-CAUSAL Enterprise”, which was held at the Harvard T.H. Chan School of Public Health with speakers from both the VA and CAUSALab.