DHHS/PHS/FDA/Office Of Facilities, Acquisition, And Central Services, Division of Contracts and Program Management, HFA-512(COB), 5600 Fishers Lane, Rockville, MD 20857

B -- GENETIC RISK FACTORS FOR TRAMADOL-RELATED SEIZURES: A MOLECULAR EPIDEMIOLOGIC STUDY SOL B21045-00-98 DUE 082598 POC Trudy Dartouzos, Contract Specialist, ph: 301/827-7165, fax: 301/827-7103 See Note #1. The Food and Drug Administration [FDA], Center for Drug Evaluation and Research [CDER] intends to award a purchase order for professional services. Scope of Work is as follows: Historical ongoing cohort study performed by United Health Care [UHC] and the University of Washington. 1] all pharmacy records including prescription for tramadol between January 1, 1995 and December 31, 1996; 2] stratified random sample of all members of concurrenty enrolled, frequency-matched in a 4:1 ratio to the users of tramadol by age, sex, period of enrollment, and health care plan. Physician and hospital discharge claims shall be assessed for services between March 1, 1995 and December 31, 1996 for claims with diagnoses suggestive of seizure disorders. All claims for physician services, emergency service and inpatient hospitalizations containing one of the following ICD-9-CM diagnosis codes: 780.3 [convulsions], 345.0-345.9 [epilepsy] or 333.2 [progressive myoclonus] shall be included. Second stage: nested case-control study. Patients who have any claim for one of the specified diagnosis codes shall be identified as cases. Medical records of cases shall be reviewed, confirmed and additional data on risk factors for tramadol-associated seizures, e.g., history, comorbid conditions, timing relative to seizure event. The proposed genotyping study would be an addition to the ongoing pharmacoepidemiology study. The CYP2D6 genotype for cases and controls shall be determined. Study subjects shall be recruited to provide blood samples from which DNA can be extracted for the genotype assay. This data shall be merged with ongoing pharmacoepidemiology study and the CYP2D6 genotype and shall become additional covariate in a logistic regression analysis. Epidemiologists at UHC and FDA shall collaboratively develop the protocol for recruiting subjects, obtaining consent, and communicating results of genotype assay to study participants. UHC shall be responsible for recruiting study subjects, obtaining IRB approval and consent, collecting blood specimens, shipping specimens to the FDA Laboratory and notifying study subjects of their CYP2D6 assay results. DNA extraction and the CYP2D6 genotype assay shall be performed at the FDA Laboratory. Data for the CYP2D6 genotype and control study will be merged with the analysis data set for the on-going case-control study. Assuming power of 80%, a one-tailed test with p-value of 0.05, and 2 controls per case, the study will require 33 cases and 66 controls to detect an odds ratio of 5.0. Written quotes due by 2:00 p.m. 8/25/98. Posted 08/06/98 (W-SN233749). (0218)

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