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Principal Investigator: Tobias Gerhard
Organization: RUTGERS BIOMEDICAL AND HEALTH SCIENCES
Fiscal Year: 2024
Award: $518,903
Funding agency: National Institute on Aging
Despite almost complete absence of adequate data from head-to-head randomized controlled trials,
treatment guidelines and prescription drug insurance formularies typically consider individual drugs within
medication classes as equally effective and equally safe. Yet, incorrect assumptions regarding therapeutic
exchangeability expose patients to suboptimal treatments and adverse clinical outcomes, particularly older
adults, who are disproportionately affected by chronic conditions and are the largest per capita consumers of
prescription medications. Despite its substantial clinical and economic implications, therapeutic exchangeability
remains remarkably understudied and represents a problem without a feasible current solution. We thus
propose a novel and feasible approach to evaluate the therapeutic exchangeability of same-class drugs. The
proposed studies will take advantage of natural experiments created by the structure of the Medicare Part D
drug benefit and the variable financial incentives that Part D plans receive from manufacturers. Due to plan-
specific formulary management strategies, Part D enrollees initiating a new medication often face substantially
different out-of-pocket costs for alternative drugs within the same class. The differences in out-of-pocket costs
among alternative same-class drugs among the hundreds of Part D plans will serve as instrumental variables
(IVs). Because these financial incentives strongly affect the choice of one drug of a class over another and are
independent of the patients’ clinical characteristics (as demonstrated by strong preliminary data), they facilitate
valid IV estimation. Outcome validation from primary medical records and cause of death data from the
National Death Index further improve the rigor of the study. Using existing data on >22 million Medicare beneficiaries, the proposed study will examine 4 carefully selected drug classes to establish a new methodological
framework for the systematic assessment of within-class therapeutic exchangeability from observational data:
1) direct oral anticoagulants (DOACs) for stroke prevention in atrial fibrillation or atrial flutter, 2) dipeptidyl
peptidase 4-inhibitors (DPP-4s) for type 2 diabetes, 3) high potency statins for secondary prevention of atherosclerotic cardiovascular (CV) disease, and 4) sodium-glucose co-transporter-2 inhibitors (SGLT-2s) for type 2
diabetes. These were selected based on explicit criteria: high rates of use in Part D beneficiaries, uncertainty
about therapeutic exchangeability within the class, sufficient variation in out-of-pocket costs among alternative
agents, and ability to validly measure outcomes in Medicare claims. We included examples with strong priors
against (DPP-4s and CV outcomes) and for (SGLT-2s and amputations) within-class differences to show we
can reproduce expected findings, and others for which differences are uncertain (e.g., DOACs and ischemic
stroke). This proposal begins a highly promising novel line of work to feasibly generate valid and critically
needed evidence on therapeutic exchangeability within widely-used drug classes among older adults, serve as
the basis for future confirmatory studies, and improve clinical medicine, patient outcomes, and public health.
Terms: <3-hydroxy-3-methylglutaryl coenzyme A Inhibitors><Adult-Onset Diabetes Mellitus><Affect><Amputation><Anticoagulant Agents><Anticoagulant Drugs><Anticoagulants><Area><Atherosclerosis><Atherosclerotic Cardiovascular Disease><Atrial Fibrillation><Atrial Flutter><Auricular Fibrillation><Auricular Flutter><Bioequivalence><Brain hemorrhage><Cardiovascular><Cardiovascular Body System><Cardiovascular Diseases><Cardiovascular Organ System><Cardiovascular system><Cause of Death><Cessation of life><Characteristics><Chronic><Clinical><Clinical Equivalency><Clinical Medical Sciences><Clinical Medicine><Co-Transporters><Cost Savings><D-Glucose><Data><Death><Development and Research><Dextrose><Dipeptidyl Aminopeptidases><Dipeptidyl Peptidases><Dipeptidylpeptide Hydrolases><Disease><Disorder><Drug Insurance><Drug Prescribing><Drug Prescriptions><Drug usage><Drugs><Economics><Enrollment><Ensure><Event><Face><Formularies><Future><Generic Equivalency><Glucose><HMG-CoA Reductase Inhibitors><HMG-CoA Statins><Head><Health Care Systems><Health Insurance for Aged and Disabled, Title 18><Health Insurance for Disabled Title 18><Healthcare Systems><Heart Vascular><Heart failure><Hydroxymethylglutaryl CoenzymeA Reductase Inhibitors><Hydroxymethylglutaryl-CoA Inhibitors><Hydroxymethylglutaryl-CoA Reductase Inhibitors><Hydroxymethylglutaryl-Coenzyme A Inhibitors><Individual><Ischemic Stroke><Ketosis-Resistant Diabetes Mellitus><Knee><Knowledge><Light><Manufacturer><Marketing><Maturity-Onset Diabetes Mellitus><Measures><Medical Records><Medicare><Medicare claim><Medication><Meta-Analysis><Methodology><Methods><NIDDM><Na element><Natural experiment><Non-Insulin Dependent Diabetes><Non-Insulin-Dependent Diabetes Mellitus><Noninsulin Dependent Diabetes><Noninsulin Dependent Diabetes Mellitus><Oral><Out-of-Pocket Expense><Outcome><Outcome Measure><Patient outcome><Patient-Centered Outcomes><Patient-Focused Outcomes><Patients><Pharmaceutical Preparations><Photoradiation><Population><Privatization><Process><Public Health><R & D><R&D><Randomized, Controlled Trials><Research><Research Design><Risk><Secondary Prevention><Slow-Onset Diabetes Mellitus><Sodium><Stable Diabetes Mellitus><Stroke prevention><Structure><Study Type><T2 DM><T2D><T2DM><Therapeutic><Therapeutic Equivalency><Title 18><Type 2 Diabetes Mellitus><Type 2 diabetes><Type II Diabetes Mellitus><Type II diabetes><Uncertainty><Uncovered Medical Expenses><Uncovered Uninsured Medical Expense><Uninsured Medical Expense><Update><Validation><Variant><Variation><Withdrawal><Work><adult onset diabetes><atheromatosis><atherosclerotic disease><atherosclerotic vascular disease><atorvastatin><beneficiary><bleeding in brain><blood thinner><cardiac failure><cardiovascular disorder><circulatory system><clinical effect><clinical relevance><clinically relevant><comparative><comparative effectiveness study><data resource><design><designing><doubt><drug bioequivalence><drug bioequivalent><drug development><drug use><drug/agent><economic><economic implication><economic incentive><enroll><evidence base><faces><facial><financial incentive><financial reward><health insurance for disabled><hemorrhagic stroke><high risk><improved><indexing><inhibitor><innovate><innovation><innovative><ketosis resistant diabetes><lipitor><maturity onset diabetes><measurable outcome><medical expenses not covered by insurance><medication prescription><monetary incentive><new approaches><novel><novel approaches><novel strategies><novel strategy><older adult><older adulthood><out-of-pocket costs><out-of-pocket health care costs><outcome measurement><patient oriented outcomes><prescribed medication><prevent stroke><randomized control trial><research and development><risk for stroke><risk of stroke><rosuvastatin><stroke risk><study design><symporter><thrombopoiesis inhibitor><total medical expenditure><treatment guidelines><type 2 DM><type II DM><type two diabetes><validations>