TY - JOUR
T1 - Methods for identifying long-term adverse effects of treatment in patients with eye diseases
T2 - The Systemic Immunosuppressive Therapy for Eye Diseases (SITE) Cohort Study
AU - Kempen, John H.
AU - Daniel, Ebenezer
AU - Gangaputra, Sapna
AU - Dreger, Kurt
AU - Jabs, Douglas A.
AU - Kaçmaz, R. Oktay
AU - Pujari, Siddharth S.
AU - Anzaar, Fahd
AU - Foster, C. Stephen
AU - Helzlsouer, Kathy J.
AU - Levy-Clarke, Grace A.
AU - Nussenblatt, Robert B.
AU - Liesegang, Teresa
AU - Rosenbaum, James T.
AU - Suhler, Eric B.
N1 - Funding Information:
This study is supported primarily by National Eye Institute Grant EY014943 (Dr. Kempen). Additional support is provided by the Paul and Evanina Mackall Foundation and Research to Prevent Blindness. Drs. Jabs and Rosenbaum are recipients of Research to Prevent Blindness Senior Scientific Investigator Awards. Drs. Levy-Clarke and Nussenblatt are supported by intramural funds of the National Eye Institute. None of the sponsors had any role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; nor in the preparation, review, and approval of this manuscript.
PY - 2008/1
Y1 - 2008/1
N2 - Purpose: To evaluate potential epidemiologic methods for studying long-term effects of immunosuppression on the risk of mortality and fatal malignancy, and present the methodological details of the Systemic Immunosuppressive Therapy for Eye Diseases (SITE) Cohort Study. Methods: Advantages and disadvantages of potential study designs for evaluating rare, late-occurring events are reviewed, and the SITE Cohort Study approach is presented. Results: The randomized, controlled trial is the most robust method for evaluating treatment effects, but long study duration, high costs, and ethical concerns when studying toxicity limit its use in this setting. Retrospective cohort studies are potentially more cost-effective and timely, if records exist providing the desired information over sufficient follow-up time in the past. Case-control methods require extremely large sample sizes to evaluate risk associated with rare exposures, and recall bias is problematic when studying mortality. The SITE Cohort Study is a retrospective cohort study. Past use of antimetabolites, T-cell inhibitors, alkylating agents, and other immunosuppressives is ascertained from medical records of ∼9,250 ocular inflammation patients at five tertiary centers over up to 30 years. Mortality and cause-specific mortality outcomes over ∼100,000 person-years are ascertained using the National Death Index. Immunosuppressed and non-immunosuppressed groups of patients are compared with each other and general population mortality rates from US vital statistics. Calculated detectable differences for mortality/fatal malignancy with respect to the general population are 22%/49% for antimetabolites, 28%/62% for T-cell inhibitors, and 36%/81% for alkylating agents. Conclusions: Information from the SITE Cohort Study should clarify whether use of these immunosuppressive drugs for ocular inflammation increases the risk of mortality and fatal cancer. This epidemiologic approach may be useful for evaluating long-term risks of systemic therapies for other ocular diseases.
AB - Purpose: To evaluate potential epidemiologic methods for studying long-term effects of immunosuppression on the risk of mortality and fatal malignancy, and present the methodological details of the Systemic Immunosuppressive Therapy for Eye Diseases (SITE) Cohort Study. Methods: Advantages and disadvantages of potential study designs for evaluating rare, late-occurring events are reviewed, and the SITE Cohort Study approach is presented. Results: The randomized, controlled trial is the most robust method for evaluating treatment effects, but long study duration, high costs, and ethical concerns when studying toxicity limit its use in this setting. Retrospective cohort studies are potentially more cost-effective and timely, if records exist providing the desired information over sufficient follow-up time in the past. Case-control methods require extremely large sample sizes to evaluate risk associated with rare exposures, and recall bias is problematic when studying mortality. The SITE Cohort Study is a retrospective cohort study. Past use of antimetabolites, T-cell inhibitors, alkylating agents, and other immunosuppressives is ascertained from medical records of ∼9,250 ocular inflammation patients at five tertiary centers over up to 30 years. Mortality and cause-specific mortality outcomes over ∼100,000 person-years are ascertained using the National Death Index. Immunosuppressed and non-immunosuppressed groups of patients are compared with each other and general population mortality rates from US vital statistics. Calculated detectable differences for mortality/fatal malignancy with respect to the general population are 22%/49% for antimetabolites, 28%/62% for T-cell inhibitors, and 36%/81% for alkylating agents. Conclusions: Information from the SITE Cohort Study should clarify whether use of these immunosuppressive drugs for ocular inflammation increases the risk of mortality and fatal cancer. This epidemiologic approach may be useful for evaluating long-term risks of systemic therapies for other ocular diseases.
KW - Cancer
KW - Cohort study
KW - Immunosuppression
KW - Mortality
KW - Ocular inflammation
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U2 - 10.1080/09286580701585892
DO - 10.1080/09286580701585892
M3 - Review article
C2 - 18300089
AN - SCOPUS:39749198170
SN - 0928-6586
VL - 15
SP - 47
EP - 55
JO - Ophthalmic Epidemiology
JF - Ophthalmic Epidemiology
IS - 1
ER -