Assessments of barriers to dissemination of serious adverse drug reaction (sADR) information are important for patient safety. Timely information dissemination on sADRs is important for oncology drugs, as they are toxic to normal and malignant cells, have high sADR rates, and often receive accelerated approval and/or priority review. Recently, the Food and Drug Administration (FDA) has approved tyrosine kinase inhibitors (TKIs), an important novel drug class administered for chronic mylogenous leukemia, gastrointestinal stromal tumors, renal cell cancers, and hepatocellular carcinoma. One concern is that drugs that receive accelerated approval or priority review are associated with sADRs not reported in a timely manner. Our objective is to develop the Southern Oncology Network on Adverse Reactions (SONAR) to evaluate sADRs for TKIs and DECREASE the duration of time between sADR identification and FDA/sponsor actions. The work builds on our identification of 50 sADRs, our sub-award from ERG assisting FDA's Center for Drug Evaluation and Research, our collaboration with former Connecticut Attorney General Richard Blumenthal that decreased the time-lag between thalidomide-sADR identification and sponsor/FDA safety-actions by several years, and FDA interest in TKI-associated cardiotoxicity. Our prior work, supported by five R01s, led to major publications, Black Box warnings, Dear Doctor letters, and changes in use of block-buster pharmaceuticals (e.g. erythropoietin/darbepoetin).
Our aims are to: identify, evaluate, and report case information for TKI-associated cardiotoxicity and other sADRs; identify factors associated with shorter time periods for identification/dissemination of sADR information; develop a novel approach to streamlining sADR information dissemination (building on our successful pilot effort); and participate in a FDA initiative that will link molecular toxic target studies (basic science) and organ-level toxicity (clinical science), with TKI-associated cardiotoxicity being the first area of study. We will disseminate brief reports for 25 to 50 TKI-associated sADRs and Citizen's Petitions to the FDA for sADRS for which our consultants identify as candidates for Black Box warnings or Dear Doctor letters (translating research into policy). The second component will be hypothesis driven, identifying factors associated with delayed sADR identification/reporting. The proposed innovative study will be the first to systematically attempt to shorten the six to seven year time lag between identification and reporting of oncology drug- associated sADRs and the first collaboration that provides information for FDA-led investigation of biologic and clinical aspects of a sADR involving an entire drug class.

Public Health Relevance

The Study of Oncology-related Adverse Reactions (SONAR) project will identify, evaluate, and report important safety information for a novel class of anti-cancer agents, tyrosine kinase inhibitors. Also, as part of hypothesis testing research, the project seeks to identify factors associated with delayed identification of serious adverse drug reactions associated with these agents as well as delays in dissemination of the relevant safety information to the medical community. As such, this will be the first study to systematically evaluate factors associated with delays in identification and reporting of serious adverse drug reactions associated with cancer agents.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
4R01CA165609-05
Application #
9125777
Study Section
Health Services Organization and Delivery Study Section (HSOD)
Program Officer
Castro, Kathleen M
Project Start
2012-08-01
Project End
2017-05-31
Budget Start
2016-06-01
Budget End
2017-05-31
Support Year
5
Fiscal Year
2016
Total Cost
Indirect Cost
Name
University of South Carolina at Columbia
Department
Other Health Professions
Type
Schools of Pharmacy
DUNS #
041387846
City
Columbia
State
SC
Country
United States
Zip Code
29208
Bennett, Charles L; Berger, Joseph R; Sartor, Oliver et al. (2018) Progressive multi-focal leucoencephalopathy among ibrutinib-treated persons with chronic lymphocytic leukaemia. Br J Haematol 180:301-304
Noxon, Virginia; Knopf, Kevin B; Norris, LeAnn B et al. (2017) Tale of Two Erythropoiesis-Stimulating Agents: Utilization, Dosing, Litigation, and Costs of Darbepoetin and Epoetin Among South Carolina Medicaid-Covered Patients With Cancer and Chemotherapy-Induced Anemia. J Oncol Pract 13:e562-e573
Yoshii, Yumi; Fujimura, Yoshihiro; Bennett, Charles L et al. (2017) Implementation of a rapid assay of ADAMTS13 activity was associated with improved 30-day survival rate in patients with acquired primary thrombotic thrombocytopenic purpura who received platelet transfusions. Transfusion 57:2045-2053
Hama, R; Bennett, C L (2017) The mechanisms of sudden-onset type adverse reactions to oseltamivir. Acta Neurol Scand 135:148-160
Bian, John; Chen, Brian; Hershman, Dawn L et al. (2017) Effects of the US Food and Drug Administration Boxed Warning of Erythropoietin-Stimulating Agents on Utilization and Adverse Outcome. J Clin Oncol 35:1945-1951
Lane, Jordan D; Friedberg, Mark W; Bennett, Charles L (2016) Associations Between Industry Sponsorship and Results of Cost-effectiveness Analyses of Drugs Used in Breast Cancer Treatment. JAMA Oncol 2:274-6
Yang, Y Tony; Chen, Brian; Bennett, Charles L (2016) Federal 340B Program Payment Scheme for Drugs Designated As Orphan Products: Congressional Clarification Needed to Close the Government-Industry Revolving Door. J Clin Oncol 34:4320-4322
Hermanson, Terhi; Bennett, Charles L; Macdougall, Iain C (2016) Peginesatide for the treatment of anemia due to chronic kidney disease - an unfulfilled promise. Expert Opin Drug Saf 15:1421-6
Chen, Brian K; Yang, Y Tony; Cheng, Xi et al. (2016) Petitioning the FDA to Improve Pharmaceutical, Device and Public Health Safety by Ordinary Citizens: A Descriptive Analysis. PLoS One 11:e0155259
Riches, M L; Trifilio, S; Chen, M et al. (2016) Risk factors and impact of non-Aspergillus mold infections following allogeneic HCT: a CIBMTR infection and immune reconstitution analysis. Bone Marrow Transplant 51:277-82

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