The implementation of clinical practice electronic records will provide access to comprehensive data of outcomes in response to clinical interventions for large populations. Analyzed appropriately, this information compiled into databases will have enormous potential to assess treatment effectiveness, both expanding and complementing the results of Randomized Controlled Trials (RCTs). However, because of pitfalls with observational Studies and validity of data from clinical records, proof of principle is needed prior to capitalizing appropriately on the enormous potential of this data. Our long-term goal is to determine whether and how non-experimental data from an electronic Ambulatory Medical Record Database can be used to reliably inform the practice of medicine. This application will examine the validity of Observational Studies using data from the UK General Practice Research Database (GPRD) to assess treatment effectiveness based on rigorous comparisons with published RCTs of cardiovascular disease. Each GPRD Study will use a modeled prospective cohort design that, to the extent possible, will reconstruct the RCT with the exception of randomization, by employing similar inclusion/exclusion criteria, treatment protocol and outcome measures. Outcomes will be analyzed by adjustment for measured confounders using propensity scores and/or multivariable regression. We also will test whether specific study characteristics predict the likelihood for obtaining a valid result with a GPRD Study. Therefore the aggregated results from 20 RCTGPRD comparative studies will be examined for predictors of concordance. If individual GPRD Studies are concordant, they will be repeated using broader entry criteria in order to examine their utility to expand generalizability. The expanded GPRD study will be compared with the initial restricted Study and with meta-analyses relevant to the comparable RCT to examine their usefulness for this purpose. Thus the Specific Aims of this study will be to assess: 1. Concordance between outcomes to therapy when GPRD Studies are subjected to rigorous comparison with comparable published RCTs of cardiovascular disease, 2. Whether particular characteristics predict concordance (or lack thereof) between results of RCTs and GPRD Studies 3. Whether GPRD Studies can verify as well as expand the generalizability of findings from RCTs.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL073911-02
Application #
6776421
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Program Officer
Fabsitz, Richard
Project Start
2003-07-15
Project End
2007-06-30
Budget Start
2004-07-01
Budget End
2005-06-30
Support Year
2
Fiscal Year
2004
Total Cost
$657,770
Indirect Cost
Name
University of Pennsylvania
Department
Biostatistics & Other Math Sci
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Tannen, Richard L; Weiner, Mark G; Xie, Dawei (2009) Use of primary care electronic medical record database in drug efficacy research on cardiovascular outcomes: comparison of database and randomised controlled trial findings. BMJ 338:b81
Tannen, Richard L; Weiner, Mark G; Xie, Dawei et al. (2008) Perspectives on hormone replacement therapy: the Women's Health Initiative and new observational studies sampling the overall population. Fertil Steril 90:258-64
Weiner, Mark G; Barnhart, Kurt; Xie, Dawei et al. (2008) Hormone therapy and coronary heart disease in young women. Menopause 15:86-93
Weiner, Mark G; Xie, Dawei; Tannen, Richard L (2008) Replication of the Scandinavian Simvastatin Survival Study using a primary care medical record database prompted exploration of a new method to address unmeasured confounding. Pharmacoepidemiol Drug Saf 17:661-70
Tannen, Richard L; Weiner, Mark G; Xie, Dawei (2008) Replicated studies of two randomized trials of angiotensin-converting enzyme inhibitors: further empiric validation of the 'prior event rate ratio'to adjust for unmeasured confounding by indication. Pharmacoepidemiol Drug Saf 17:671-85
Tannen, Richard L; Weiner, Mark G; Xie, Dawei et al. (2007) A simulation using data from a primary care practice database closely replicated the women's health initiative trial. J Clin Epidemiol 60:686-95
Tannen, Richard L; Weiner, Mark G; Xie, Dawei et al. (2007) Estrogen affects post-menopausal women differently than estrogen plus progestin replacement therapy. Hum Reprod 22:1769-77
Tannen, Richard L; Weiner, Mark G; Marcus, Sue M (2006) Simulation of the Syst-Eur randomized control trial using a primary care electronic medical record was feasible. J Clin Epidemiol 59:254-64