Tufts Center for the Study of Drug Development

About: Tufts Center for the Study of Drug Development is a based out in . It is known for research contribution in the topics: Drug development & Clinical trial. The organization has 78 authors who have published 258 publications receiving 16047 citations.

Dearth of clinically useful diagnostics limits growth of personalized medicine

Abstract: Pharmacogenomics explores the ways in which genetic variations can be used to predict whether an individual patient will benefit from a drug, have a bad response or no response at all [1]. Knowledge of genetic variance can guide drug development or dosing tailored to an individual’s specific circumstances. This, in turn, may reduce the chance of adverse drug reactions, maximize the probability of better health outcomes and diminish costs [2,3].

Personalized medicine: are payers the weak link?

Abstract: there is no codevelopment of tests. Tests are developed post hoc as a way of personalizing a drug, such as in the examples of abacavir and warfarin [8]. Despite the success stories, pharmaco genomics has had limited impact on clinical practice to date. The list of FDA/EMA-approved companion diagnostics is still relatively short, perhaps a dozen or so. There are significant clinical, financial and ethical barriers to the successful implementation of pharmacogenomics. Scientifically, the process of biomarker discovery and validation has been disappointingly slow. Additionally, regulatory and reimbursement issues have been problematic, particularly with respect to companion diagnostics, but also drugs that lack clinically effective diagnostics. To illustrate this point, gefitinib only works in approximately 10% of patients with advanced non-small-cell lung cancer. In June 2009, the FDA partially withdrew the drug, no longer allowing its prescription to new non-small-cell lung cancer patients, as no useful EGF receptor (EGFR) biomarker test is (yet) commercialized in the USA to pinpoint positive responders. As a result, gefitinib has encountered considerable market access issues, as payers are quite reluctant to reimburse. Even with FDA/EMA-approved biomarker tests lingering questions persist regarding their clinical effectiveness. A case in point is warfarin, which illustrates the acute translational gap that exists between knowledge and application. Tests suggest patients deficient in a certain enzyme activity (CYP2C9) may require a lower warfarin dose or more frequent monitoring and may be at risk of bleeding episodes. Since 2007, the FDA has been recommending genotyping for all patients being prescribed warfarin. In spite of this, in April 2009, the Centers for Medicare and Medicaid Services (CMS) decided not to routinely pay for genetic tests intended to help doctors determine Pharmacogenomics explores the ways in which genetic variations can be used to predict whether an individual patient will benefit from a drug, have a bad response or no response at all. Accordingly, therapies may be tailored to certain genetic characteristics of individual patients or subpopulations, drawing on data gathered from a variety of sources, including tests for biomarkers [1]. Knowledge of genetic variance can guide the selection of appropriate drugs or dosing tailored to an individual’s specific circumstances. This, in turn, may reduce the chance of adverse events, maximize the probability of better health outcomes and diminish costs [2,3]. In some instances, tests select which patients should or should not take a particular medication. For example, a test is used in conjunction with the breast cancer biologic trastuzumab to detect patients whose tumors overexpress HER2 protein [4,5]. In other cases, tests are used to predict the probability of adverse events associated with the use of a particular drug [6]. For example, there is a test which links hypersensitivity reactions to the HIV/AIDS drug abacavir to a specific genotype. Furthermore, there are tests which suggest ways to modify dosing in patients with an innately poor ability to metabolize a certain drug. In the case of warfarin, for instance, tests detect variations in the way individuals metabolize the blood-thinning agent. This may help to optimize dosing. Some personalized medicines are developed pharmacogenomically, concurrently with companion diagnostics. Trastuzumab was codeveloped with a pharmacogenomics test, which was US FDA/EMA approved and recommended prior to prescribing. There are also instances, such as the cancer biologic cetuximab, when a drug was codeveloped with a test but testing is not recommended by any regulatory authority prior to prescribing [7]. However, in most cases, at present “...in order to achieve widespread favorable reimbursement and clinical uptake for genetic tests and targeted therapies, manufacturers will need to bring more, and better, clinical evidence to the market place...”

Impact of Disease Management on Cost-Effectiveness of Medicare Spending

Abstract: Findings from the third annual Tufts Center for the Study of Drug Development survey of 22 leading disease and pharmacy benefits managers suggest that incorporation of disease management into Medicare would lower hospital inpatient costs. However, it is unclear whether hospital cost savings would be sufficient to offset increases in pharmacy, physician, and outpatient expenditures as a result of an added combination disease management and pharmacy benefit. Furthermore, the survey indicates that the Centers for Medicare & Medicaid Services (CMS) would likely struggle in recruiting disease managers due to their limited enrollment of Medicare beneficiaries, relative inexperience with contracts that put disease managers at risk, and only sporadic use of randomized design studies to test and prove the efficacy of disease management interventions. Thirteen of the 22 survey respondents are currently considered early compilers per accreditation standards developed by the National Committee on Quality Assurance. However, none of the 22 survey respondents compty with the stringent CMS requirements described in the solicitation for the 2002 disease management demonstration.