Research on Adverse Drug events And Reports
Encyclopedia
Research on Adverse Drug events And Reports (RADAR) is a pharmacovigilance
team of 25 doctors who receive calls about possible adverse drug reaction
s (ADR) and investigate. RADAR is based at Northwestern
's Feinberg School of Medicine
. RADAR is led by Dennis West. Though it was without funding for its first four years, RADAR has raised about $12 million through grants from the National Institutes of Health
, the American Cancer Society
and other such institutions. Its work has identified safety problems with 33 drugs. Adverse drug events are a serious health problem.
signal is present in the population of those exposed to that drug.
involved multiple biological system and included thrombotic thrombocytopenic purpura
(TTP) (ticlopidine
and clopidogrel
), thromboembolism (thalidomide
and lenalidomide
), hepatic failure (gemtuzumab and nevirapine), hypersensitivity
(drug eluting coronary arterial stents
), pure red-cell aplasia
(PRCA) (epoetin), vision changes (amiodarone
, sildenafil
, and tadalafil
), late thrombotic events
(drug eluting cardiac stents
), leukemia
(G-CSF), and interstitial pneumonitis (gemcitabine). For each individual ADR, the number of unique event reports collected by RADAR ranged from 0 to 96. Twenty-seven sADRs were associated with drugs and four were associated with a device.
as well as more focused databases such as the Medicare
-SEER database. Hypothesis-driven active surveillance of a few hundred safety reports serves as the underlying conceptual framework of RADAR pharmacovigilance
. Fewer than 20 individual ADR reports led to RADAR investigators identifying safety signals for the majority of the ADRs described to date. Despite a small number of reports for each ADR, causality
assessments have been supported by pathology
studies, antibody
studies, and autopsies. For example, the initial description of thrombotic thrombocytopenic purpura
associated with clopidogrel
included only 11 cases.
present. These analyses synthesize the various sources of statistical information on the presence of adverse reactions to these drugs and assess whether the actual risk is in line with studies.
Pharmacovigilance
Pharmacovigilance is the pharmacological science relating to the detection, assessment, understanding and prevention of adverse effects, particularly long term and short term side effects of medicines...
team of 25 doctors who receive calls about possible adverse drug reaction
Adverse drug reaction
An adverse drug reaction is an expression that describes harm associated with the use of given medications at a normal dosage. ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs...
s (ADR) and investigate. RADAR is based at Northwestern
Northwestern University
Northwestern University is a private research university in Evanston and Chicago, Illinois, USA. Northwestern has eleven undergraduate, graduate, and professional schools offering 124 undergraduate degrees and 145 graduate and professional degrees....
's Feinberg School of Medicine
Feinberg School of Medicine
Northwestern University Feinberg School of Medicine, located in the Streeterville neighborhood of Chicago, Illinois and situated near Lake Michigan and the Magnificent Mile, is one of Northwestern University's 11 schools and colleges...
. RADAR is led by Dennis West. Though it was without funding for its first four years, RADAR has raised about $12 million through grants from the National Institutes of Health
National Institutes of Health
The National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation...
, the American Cancer Society
American Cancer Society
The American Cancer Society is the "nationwide community-based voluntary health organization" dedicated, in their own words, "to eliminating cancer as a major health problem by preventing cancer, saving lives, and diminishing suffering from cancer, through research, education, advocacy, and...
and other such institutions. Its work has identified safety problems with 33 drugs. Adverse drug events are a serious health problem.
Aims
The aims of RADAR are to disseminate safety reports for serious adverse drug reactions (sADRs) and to identify barriers to identification and reporting of these clinical events. Investigators have developed a well-coordinated system to accurately compile case report information on sADRs and to identify milestones associated with identification and reporting of the relevant ADR information. This ADR identification system allows us to amass pertinent sADR information from a diverse set of data sources in order to identify and report sADRs in a timely and thorough manner. With increasingly shortened review periods, post-marketing surveillance for sADRs has become very important. In some instances, initial cases are identified at hospital case conferences and reported to the U.S. Food and Drug Administration (FDA) or to the pharmaceutical manufacturer. The RADAR methodology relies on initial recognition of these “sentinel” cases that then prompts hypothesis–driven inquiries as to whether an unrecognized adverse drug eventAdverse drug reaction
An adverse drug reaction is an expression that describes harm associated with the use of given medications at a normal dosage. ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs...
signal is present in the population of those exposed to that drug.
Results
Between 1998 and 2007, 33 serious adverse drug or device reactions have been reported by RADAR investigators. The toxicitiesToxicity
Toxicity is the degree to which a substance can damage a living or non-living organisms. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a substructure of the organism, such as a cell or an organ , such as the liver...
involved multiple biological system and included thrombotic thrombocytopenic purpura
Thrombotic thrombocytopenic purpura
Thrombotic thrombocytopenic purpura is a rare disorder of the blood-coagulation system, causing extensive microscopic thromboses to form in small blood vessels throughout the body...
(TTP) (ticlopidine
Ticlopidine
Ticlopidine is an antiplatelet drug in the thienopyridine family. Like clopidogrel, it is an adenosine diphosphate receptor inhibitor. It is used in patients in whom aspirin is not tolerated, or in whom dual antiplatelet therapy is desirable...
and clopidogrel
Clopidogrel
Clopidogrel is an oral, thienopyridine class antiplatelet agent used to inhibit blood clots in coronary artery disease, peripheral vascular disease, and cerebrovascular disease. It is marketed by Bristol-Myers Squibb and Sanofi-Aventis under the trade name Plavix. The drug works by irreversibly...
), thromboembolism (thalidomide
Thalidomide
Thalidomide was introduced as a sedative drug in the late 1950s that was typically used to cure morning sickness. In 1961, it was withdrawn due to teratogenicity and neuropathy. There is now a growing clinical interest in thalidomide, and it is introduced as an immunomodulatory agent used...
and lenalidomide
Lenalidomide
Lenalidomide , initially known as CC-5013 and marketed as Revlimid by Celgene, is a derivative of thalidomide introduced in 2004....
), hepatic failure (gemtuzumab and nevirapine), hypersensitivity
Hypersensitivity
Hypersensitivity refers to undesirable reactions produced by the normal immune system, including allergies and autoimmunity. These reactions may be damaging, uncomfortable, or occasionally fatal. Hypersensitivity reactions require a pre-sensitized state of the host. The four-group classification...
(drug eluting coronary arterial stents
Drug-eluting stent
A drug-eluting stent ' is a peripheral or coronary stent placed into narrowed, diseased peripheral or coronary arteries that slowly releases a drug to block cell proliferation. This prevents fibrosis that, together with clots , could otherwise block the stented artery, a process called restenosis...
), pure red-cell aplasia
Acquired pure red cell aplasia
Pure red cell aplasia or erythroblastopenia refers to a type of anemia affecting the precursors to red blood cells but not to white blood cells. In PRCA, the bone marrow ceases to produce red blood cells...
(PRCA) (epoetin), vision changes (amiodarone
Amiodarone
Amiodarone is an antiarrhythmic agent used for various types of tachyarrhythmias , both ventricular and supraventricular arrhythmias. Discovered in 1961, it was not approved for use in the United States until 1985...
, sildenafil
Sildenafil
Sildenafil citrate, sold as Viagra, Revatio and under various other trade names, is a drug used to treat erectile dysfunction and pulmonary arterial hypertension . It was originally developed by British scientists and then brought to market by the US-based pharmaceutical company Pfizer...
, and tadalafil
Tadalafil
Tadalafil is a PDE5 inhibitor, currently marketed in pill form for treating erectile dysfunction under the name Cialis; and under the name Adcirca for the treatment of pulmonary arterial hypertension...
), late thrombotic events
Thrombosis
Thrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets and fibrin to form a blood clot to prevent blood loss...
(drug eluting cardiac stents
Drug-eluting stent
A drug-eluting stent ' is a peripheral or coronary stent placed into narrowed, diseased peripheral or coronary arteries that slowly releases a drug to block cell proliferation. This prevents fibrosis that, together with clots , could otherwise block the stented artery, a process called restenosis...
), leukemia
Leukemia
Leukemia or leukaemia is a type of cancer of the blood or bone marrow characterized by an abnormal increase of immature white blood cells called "blasts". Leukemia is a broad term covering a spectrum of diseases...
(G-CSF), and interstitial pneumonitis (gemcitabine). For each individual ADR, the number of unique event reports collected by RADAR ranged from 0 to 96. Twenty-seven sADRs were associated with drugs and four were associated with a device.
Methods
The success of the RADAR program has previously been largely based on the use of diverse data sources to identify, clarify, and verify ADRs. Databases, registries, clinical trials, referral centers, and case reports have all been utilized as sites of detection. In particular, RADAR has made use of reports submitted to MedWatchMedWatch
MedWatch is the Food and Drug Administration’s reporting system for an adverse event or sentinel event, founded in 1993. An adverse event is any undesirable experience associated with the use of a medical product...
as well as more focused databases such as the Medicare
Medicare (United States)
Medicare is a social insurance program administered by the United States government, providing health insurance coverage to people who are aged 65 and over; to those who are under 65 and are permanently physically disabled or who have a congenital physical disability; or to those who meet other...
-SEER database. Hypothesis-driven active surveillance of a few hundred safety reports serves as the underlying conceptual framework of RADAR pharmacovigilance
Pharmacovigilance
Pharmacovigilance is the pharmacological science relating to the detection, assessment, understanding and prevention of adverse effects, particularly long term and short term side effects of medicines...
. Fewer than 20 individual ADR reports led to RADAR investigators identifying safety signals for the majority of the ADRs described to date. Despite a small number of reports for each ADR, causality
Causality
Causality is the relationship between an event and a second event , where the second event is understood as a consequence of the first....
assessments have been supported by pathology
Pathology
Pathology is the precise study and diagnosis of disease. The word pathology is from Ancient Greek , pathos, "feeling, suffering"; and , -logia, "the study of". Pathologization, to pathologize, refers to the process of defining a condition or behavior as pathological, e.g. pathological gambling....
studies, antibody
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
studies, and autopsies. For example, the initial description of thrombotic thrombocytopenic purpura
Thrombotic thrombocytopenic purpura
Thrombotic thrombocytopenic purpura is a rare disorder of the blood-coagulation system, causing extensive microscopic thromboses to form in small blood vessels throughout the body...
associated with clopidogrel
Clopidogrel
Clopidogrel is an oral, thienopyridine class antiplatelet agent used to inhibit blood clots in coronary artery disease, peripheral vascular disease, and cerebrovascular disease. It is marketed by Bristol-Myers Squibb and Sanofi-Aventis under the trade name Plavix. The drug works by irreversibly...
included only 11 cases.
Strengths
RADAR has also identified key barriers to timely and efficiently identifying ADRs and to comprehensively reporting these findings. In particular, we identified quality concerns with MedWatch reports (the FDA’s primary source of adverse event reports) and poor quality of dissemination of adverse event findings from the FDA and the pharmaceutical sponsor. Our efforts have found that RADAR sADR identification and dissemination efforts can be as rapid as one to two years after FDA approval, in contrast to the seven years generally seen with safety efforts from the FDA and pharmaceutical sponsors. Thus, the RADAR project has developed into an important adjunct to the current pharmaceutical drug and device safety system.Specific ADR reports by RADAR
RADAR has analyzed historical data on many drugs from their initial inception, through approval by the FDA, and to thepresent. These analyses synthesize the various sources of statistical information on the presence of adverse reactions to these drugs and assess whether the actual risk is in line with studies.