The use of prescription and non-prescription drugs for prevention of chronic diseases is a central feature of the care of older adults. Randomized controlled trials assessing the effectiveness of pharmacoprevention of chronic diseases in older adults are very costly, take a long time to design and implement, and may be of limited generalizability due to selection of participants, shorter duration of treatment, and changes in therapies that occur over the course of the trial. Nonexperimental studies on beneficial and harmful effects of drugs, including studies based on administrative data that often are the only available data, however, have frequently been criticized as producing biased results. It is therefore vital to develop and apply adequate methods to reduce bias in observational studies that assess the preventive effects of medication use in older patients. Propensity scores (PSs) are an increasingly used technique to address confounding in nonexperimental research. PSs are often perceived as superior to conventional analyses in nonexperimental studies assessing the effectiveness of drugs and medical procedures. Funded by RO1 AG023178, we have assessed limitations and advantages of propensity scores (PS) in real datasets and extensive simulations and have developed novel analytic techniques based on PS since 2005. We have disseminated our results by means of oral presentations (28), posters (16), and workshops/symposia (4) at major international epidemiologic, pharmacoepidemiologic, biostatistics, and statistics meetings and in a series of 27 publications, including 9 in the highet ranked epidemiologic journal (the American Journal of Epidemiology). We have focused our research on one of the major problems of nonexperimental research of beneficial and harmful effects of drug treatments, i.e., the problem of unmeasured confounding. We previously had developed an innovative method to include additional information on confounders not measured in the main study from an external validation study combining PS and regression calibration (Propensity Score Calibration). We recently published another innovative method to deal with confounding bias by unmeasured confounders. This method is based on the assumption that patients treated contrary to prediction are more likely to have unmeasured confounders, like frailty, leading the physician to override the predicted treatment. This is the first paper ever showing a clear advantage of PS methods over conventional multivariable outcome models with respect to unmeasured confounders. The second competing continuation will build on our work over the last 7 years and extend it in the same domain - limitations and value of PSs to assess the preventive effects of medication use in older patients with a slightly changed team of researchers while keeping the same core investigators. Using new data sources, including a large random national sample of 3 million Medicare beneficiaries each for the years 2007, 20008, and 2009, we will focus on several unresolved new and distinct topics regarding the implementation of PSs and the effects of preventive drug use in the elderly.

Public Health Relevance

Drugs are a mainstay of today's healthcare. Universal access to affordable drugs with the optimal benefit to harm balance for a given individual is a major global, national, and local public and individual health goal. Despite pre-marketing proof of efficacy in randomized trials, there is little known about harms at the time of drug approval (e.g. Vioxx) and data on benefits are usually lacking for the majority of patients who will ultimately be treated, e.g., older adults with co-morbidities and co-medications. Nonexperimental post-approval studies can fill this knowledge gap on drug benefits and harms needed to make optimal treatment decisions but need to be designed carefully to be valid. Funded by NIA we have successfully developed and evaluated advanced and novel methods to increase the validity of nonexperimental post- approval studies over the last 7 years and propose to continue to do so mainly based on data on prescription drug use and diagnoses from a representative sample of approximately 3 million Medicare beneficiaries per year for the years 2007 to 2009.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG023178-09
Application #
8448605
Study Section
Neurological, Aging and Musculoskeletal Epidemiology (NAME)
Program Officer
Bhattacharyya, Partha
Project Start
2003-12-01
Project End
2015-03-31
Budget Start
2013-06-15
Budget End
2014-03-31
Support Year
9
Fiscal Year
2013
Total Cost
$302,747
Indirect Cost
$86,914
Name
University of North Carolina Chapel Hill
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Hong, Jin-Liern; Jonsson Funk, Michele; Buse, John B et al. (2017) Comparative Effect of Initiating Metformin Versus Sulfonylureas on Breast Cancer Risk in Older Women. Epidemiology 28:446-454
Wyss, Richard; Hansen, Ben B; Ellis, Alan R et al. (2017) The ""Dry-Run"" Analysis: A Method for Evaluating Risk Scores for Confounding Control. Am J Epidemiol 185:842-852
Lund, Jennifer L; Horváth-Puhó, Erzsébet; Komjáthiné Szépligeti, Szimonetta et al. (2017) Conditioning on future exposure to define study cohorts can induce bias: the case of low-dose acetylsalicylic acid and risk of major bleeding. Clin Epidemiol 9:611-626
Gokhale, Mugdha; Buse, John B; Jonsson Funk, Michele et al. (2017) No increased risk of cardiovascular events in older adults initiating dipeptidyl peptidase-4 inhibitors vs therapeutic alternatives. Diabetes Obes Metab 19:970-978
Hong, Jin-Liern; Henderson, Louise M; Jonsson Funk, Michele et al. (2017) Differential Use of Screening Mammography in Older Women Initiating Metformin versus Sulfonylurea. Pharmacoepidemiol Drug Saf 26:666-675
Zhang, Henry T; McGrath, Leah J; Wyss, Richard et al. (2017) Controlling confounding by frailty when estimating influenza vaccine effectiveness using predictors of dependency in activities of daily living. Pharmacoepidemiol Drug Saf 26:1500-1506
Zimmerman, Kanecia O; Smith, P Brian; Benjamin, Daniel K et al. (2017) Sedation, Analgesia, and Paralysis during Mechanical Ventilation of Premature Infants. J Pediatr 180:99-104.e1
Bushnell, Greta A; Stürmer, Til; White, Alice et al. (2016) Predicting persistence to antidepressant treatment in administrative claims data: Considering the influence of refill delays and prior persistence on other medications. J Affect Disord 196:138-47
Brookhart, M Alan; Freburger, Janet K; Ellis, Alan R et al. (2016) Comparative Short-term Safety of Sodium Ferric Gluconate Versus Iron Sucrose in Hemodialysis Patients. Am J Kidney Dis 67:119-27
Kinlaw, Alan C; Jonsson Funk, Michele; Steiner, Michael J et al. (2016) Trends in Pharmacotherapy for Bladder Dysfunction Among Children in the United States, 2000 to 2013. Clin Pediatr (Phila) :

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