A Brief Primer on Automated Signal Detection

2003 ◽  
Vol 37 (7-8) ◽  
pp. 1117-1123 ◽  
Author(s):  
Manfred Hauben
Keyword(s):  
Signal Detection ◽  
Adverse Drug Events ◽  
Data Extraction ◽  
Performance Characteristics ◽  
Data Sources ◽  
Drug Event ◽  
Computer Assisted ◽  
Statistical Independence ◽  
Medline Search ◽  
Advantages And Disadvantages

BACKGROUND: Statistical techniques have traditionally been underused in spontaneous reporting systems used for postmarketing surveillance of adverse drug events. Regulatory agencies, pharmaceutical companies, and drug monitoring centers have recently devoted considerable efforts to develop and implement computer-assisted automated signal detection methodologies that employ statistical theory to enhance screening efforts of expert clinical reviewers. OBJECTIVE: To provide a concise state-of-the-art review of the most commonly used automated signal detection procedures, including the underlying statistical concepts, performance characteristics, and outstanding limitations, and issues to be resolved. DATA SOURCES: Primary articles were identified by MEDLINE search (1965–December 2002) and through secondary sources. STUDY SELECTION AND DATA EXTRACTION: All of the articles identified from the data sources were evaluated and all information deemed relevant was included in this review. DATA SYNTHESIS: Commonly used methods of automated signal detection are self-contained and involve screening large databases of spontaneous adverse event reports in search of interestingly large disproportionalities or dependencies between significant variables, usually single drug–event pairs, based on an underlying model of statistical independence. The models vary according to the underlying model of statistical independence and whether additional mathematical modeling using Bayesian analysis is applied to the crude measures of disproportionality. There are many potential advantages and disadvantages of these methods, as well as significant unresolved issues related to the application of these techniques, including lack of comprehensive head-to-head comparisons in a single large transnational database, lack of prospective evaluations, and the lack of gold standard of signal detection. CONCLUSIONS: Current methods of automated signal detection are nonclinical and only highlight deviations from independence without explaining whether these deviations are due to a causal linkage or numerous potential confounders. They therefore cannot replace expert clinical reviewers, but can help them to focus attention when confronted with the difficult task of screening huge numbers of drug–event combinations for potential signals. Important questions remain to be answered about the performance characteristics of these methods. Pharmacovigilance professionals should take the time to learn the underlying mathematical concepts in order to critically evaluate accumulating experience pertaining to the relative performance characteristics of these methods that are incompletely defined.

Isoniazid-Associated Psychosis: Case Report and Review of the Literature

1993 ◽  
Vol 27 (2) ◽  
pp. 167-170 ◽  
Author(s):  
Karen A. Pallone ◽  
Morton P. Goldman ◽  
Matthew A. Fuller
Keyword(s):  
Case Report ◽  
English Language ◽  
Case Reports ◽  
Data Extraction ◽  
Data Sources ◽  
Review Of The Literature ◽  
Data Synthesis ◽  
Medline Search ◽  
Study Selection ◽  
Language Literature

Objective To describe a case of isoniazid-associated psychosis and review the incidence of this adverse effect. Data Sources Information about the patient was obtained from the medical chart. A MEDLINE search of the English-language literature published from 1950 to 1992 was conducted and Index Medicus was manually searched for current information. Study Selection All case reports describing isoniazid-associated psychosis were reviewed. Data Extraction Studies were evaluated for the use of isoniazid, symptoms of psychosis, onset of symptoms, and dosage of isoniazid. Data Synthesis The case report is compared with others reported in the literature. The incidence of isoniazid-associated psychosis is rare. Conclusions The mechanism of isoniazid-associated psychosis is uncertain. It appears that isoniazid was associated with the psychosis evident in our patient and in the cases reviewed.

5-Azacytidine and Decitabine Monotherapies of Myelodysplastic Disorders

2005 ◽  
Vol 39 (10) ◽  
pp. 1700-1709 ◽  
Author(s):  
Jim R Kuykendall
Keyword(s):  
Clinical Trials ◽  
Data Extraction ◽  
Supportive Therapy ◽  
Clinical Effectiveness ◽  
Data Sources ◽  
Hypomethylating Agents ◽  
Medline Search ◽  
Study Selection ◽  
Response To Chemotherapy ◽  
Leukemia Treatment

OBJECTIVE: To review and differentiate the pharmacology, toxicology, pharmacokinetics, and results of major clinical trials of 5-azacytidine (5-AzaC) and 5-aza-2'-deoxycytidine (decitabine) therapy of myelodysplastic disorders. DATA SOURCES: A PubMed/MEDLINE search was conducted (1966–October 2004) using the following terms: DNA methylation, myelodysplastic disorders, 5-azacytidine, and 5-aza-2'-deoxycytidine (decitabine). Additional data sources included bibliographies from identified articles and manufacturer information. STUDY SELECTION AND DATA EXTRACTION: Clinical trials for the treatment of various malignancies by hypomethylating agents were selected from data sources. All published, major clinical trials evaluating 5-AzaC or decitabine in myelodysplastic disorders and transformed myeloid leukemia treatment were included. DATA SYNTHESIS: Myelodysplastic disorders are a group of bone marrow stem cell hyperplasias and dysplasias that result in ineffective hematopoiesis. Myelodysplastic disorders and transformed leukemia have poor prognosis and minimal response to chemotherapy. DNA hypomethylating agents have been shown to improve overall response rates (increased neutrophil, leukocyte, and platelet counts), time to leukemic progression, and quality of life compared with supportive therapy. The incidence of the most common adverse effects (nausea, vomiting, myelosuppression) can be reduced by low-dose, continuous, or extended-interval infusion. CONCLUSIONS: Since appropriate dosing schedules of decitabine are being investigated, comparison of the clinical effectiveness of 5-AzaC and decitabine would be premature at this time. DNA hypomethylating agents show promise as monotherapies of myelodysplastic disorders and transformed leukemia and may be useful as a component of combination chemotherapy of various malignancies.

scholarly journals The Role of Ganciclovir for the Management of Cytomegalovirus Retinitis in HIV Patients: Pharmacological Review and Update on New Developments

1996 ◽  
Vol 7 (3) ◽  
pp. 183-194 ◽  
Author(s):  
Alice Tseng ◽  
Michelle Foisy
Keyword(s):  
English Language ◽  
Data Extraction ◽  
Clear Understanding ◽  
Medical Subject Headings ◽  
Aids Patients ◽  
Intravenous Ganciclovir ◽  
Medline Search ◽  
Advantages And Disadvantages ◽  
Cmv Retinitis

OBJECTIVE: To review the pharmacology and pharmacokinetics of intravenous, oral and intraocular ganciclovir, and to discuss the role of these various formulations in the management of cytomegalovirus (CMV) retinitis in AIDS patients.DATA SOURCES: A MEDLINE search (1987 through November 1995) of English-language literature using the main medical subject headings ‘ganciclovir’ and ‘cytomegalovirus’, and the subheading ‘acquired immunodeficiency syndrome’. Relevant articles were also selected from references of identified articles. Abstracts from recent medical conferences of infectious diseases, pharmacology and human immunodeficiency virus were screened for additional data.STUDY SELECTION AND DATA EXTRACTION: All articles and abstracts discussing the use of ganciclovir for the management or prophylaxis of CMV retinitis in AIDS patients were considered for inclusion. Pertinent information, as judged by the authors, was selected and synthesized for discussion.DATA SYNTHESIS: Ganciclovir has demonstrated virustatic activity against CMV, and is often administered 5 mg/kg intravenously every 12 h as first-line therapy for CMV retinitis. Intravenous maintenance therapy at 5 mg/kg daily is usually effective at delaying retinitis progression for approximately 60 to 70 days. Neutropenia and thrombocytopenia are observed frequently, often necessitating interruption or discontinuation of therapy. Local drug administration may delay disease progression even further, and may be considered for patients who are intolerant to or failing intravenous therapy. However, systemic ganciclovir should be encouraged to reduce the risk of developing contralateral eye or end-organ CMV disease. Oral ganciclovir at 1 g tid is almost as effective as intravenous ganciclovir 5 mg/kg/day in delaying retinitis progression and is associated with fewer line-related complications. Absorption, drug interactions, cost and compliance should also be considered.CONCLUSIONS: Until recently, ganciclovir was available only for intravenous use. Recent developments allow for intraocular and oral administration of this agent. A clear understanding of the advantages and disadvantages of these new formulations is required in order to select the most appropriate product for managing CMV retinitis in AIDS patients.

Pathophysiology and First-Line Treatment of Osteoarthritis

2002 ◽  
Vol 36 (4) ◽  
pp. 679-686 ◽  
Author(s):  
Jesse H Hogue ◽  
Tracey L Mersfelder
Keyword(s):  
Data Extraction ◽  
Treatment Options ◽  
Primary Treatment ◽  
Data Sources ◽  
Treatment Modalities ◽  
Comparable Efficacy ◽  
Antiinflammatory Drugs ◽  
Medline Search ◽  
Cox 2 ◽  
Cox 2 Inhibitors

OBJECTIVE: To review the pathophysiology of osteoarthritis (OA) and the various treatment modalities, focusing specifically on acetaminophen (APAP), nonsteroidal antiinflammatory drugs (NSAIDs), and cyclooxygenase-2 (COX-2) inhibitors as the primary treatment options. DATA SOURCES: Primary literature and tertiary references were identified by a MEDLINE search (1966–March 2001) and through other secondary sources. STUDY SELECTION AND DATA EXTRACTION: After evaluating the articles and references identified from the data sources, all the information that was judged relevant by the reviewers was included in the review article. DATA SYNTHESIS: OA is the most common joint disorder worldwide. Current research suggests that factors such as inflammation and changes in subchondral bone may play a larger role in the pathophysiology than previously thought. With this research and the development of COX-2 inhibitors, selecting the medication of choice for OA has become difficult. CONCLUSIONS: More research needs to be done before the pathophysiology of OA can be clearly determined. In the meantime, treatment should be based on clinical data and patient response. Studies have shown that APAP and NSAIDs have comparable efficacy, as do traditional NSAIDs and COX-2 inhibitors. APAP is associated with fewer toxicities than are the traditional NSAIDs. Due to their mechanism of action, the new COX-2 inhibitors should result in fewer adverse effects compared with traditional NSAIDs, but evidence from clinical trials has not been conclusive. Therefore, APAP should still be considered the drug of choice for OA.

Natalizumab for the Treatment of Multiple Sclerosis and Crohn's Disease

2005 ◽  
Vol 39 (11) ◽  
pp. 1833-1843 ◽  
Author(s):  
Kendra A Keeley ◽  
Michael P Rivey ◽  
Douglas R Allington
Keyword(s):  
Multiple Sclerosis ◽  
Inflammatory Bowel Disease ◽  
Clinical Trials ◽  
Bowel Disease ◽  
Randomized Clinical Trials ◽  
Case Reports ◽  
Data Extraction ◽  
Data Sources ◽  
Medline Search ◽  
Inflammatory Bowel

OBJECTIVE To review the pharmacology, pharmacokinetics, safety, and pivotal clinical trials for natalizumab in the treatment of multiple sclerosis (MS) and inflammatory bowel disease. DATA SOURCES A PubMed/MEDLINE search was conducted (1966–June 2005), and information was obtained from Iowa Drug Information Services. Additional data sources included meeting abstracts, bibliographies from identified articles, and information from the manufacturer. STUDY SELECTION AND DATA EXTRACTION Studies and review articles examining natalizumab were evaluated. All published, randomized clinical trials evaluating natalizumab in MS and IBD were included in this review. DATA SYNTHESIS Natalizumab is the first drug in a new class of agents called selective adhesion molecule inhibitors. It has shown promising results in MS and inflammatory bowel disease and appears superior compared with current therapies in reducing relapse rates. However, 3 recent, confirmed case reports of progressive multifocal leukoencephalopathy (PML) create concern about natalizumab's use in combination with existing therapies or in undefined patient subgroups. Natalizumab was voluntarily withdrawn from the market in March 2005 while the drug's safety is further evaluated. CONCLUSIONS Although long-term efficacy and safety of natalizumab have not been established, available data indicate that it is a novel drug for patients with MS or inflammatory bowel disease. Analysis of its possible association with PML will determine the risk–benefit evaluation and eventual place in therapy for natalizumab.

Automation in signal management in pharmacovigilance—an insight

2020 ◽  
Author(s):  
Diksha Wadhwa ◽  
Keshav Kumar ◽  
Sonali Batra ◽  
Sumit Sharma
Keyword(s):  
Health Care ◽  
Signal Detection ◽  
Adverse Drug Events ◽  
Data Extraction ◽  
Modern Society ◽  
Individual Case ◽  
Optimal Decision ◽  
Therapeutic Effects ◽  
Quality Of Data ◽  
Ideal System

Abstract Drugs are the imperial part of modern society, but along with their therapeutic effects, drugs can also cause adverse effects, which can be mild to morbid. Pharmacovigilance is the process of collection, detection, assessment, monitoring and prevention of adverse drug events in both clinical trials as well as in the post-marketing phase. The recent trends in increasing unknown adverse events, known as signals, have raised the need to develop an ideal system for monitoring and detecting the potential signals timely. The process of signal management comprises of techniques to identify individual case safety reports systematically. Automated signal detection is highly based upon the data mining of the spontaneous reporting system such as reports from health care professional, observational studies, medical literature or from social media. If a signal is not managed properly, it can become an identical risk associated with the drug which can be hazardous for the patient safety and may have fatal outcomes which may impact health care system adversely. Once a signal is detected quantitatively, it can be further processed by the signal management team for the qualitative analysis and further evaluations. The main components of automated signal detection are data extraction, data acquisition, data selection, and data analysis and data evaluation. This system must be developed in the correct format and context, which eventually emphasizes the quality of data collected and leads to the optimal decision-making based upon the scientific evaluation.

Applications of Flow Cytometry and Immunohistochemistry to Diagnostic Hematopathology

2004 ◽  
Vol 128 (9) ◽  
pp. 1004-1022 ◽  
Author(s):  
Cherie H. Dunphy
Keyword(s):  
Data Extraction ◽  
Data Sources ◽  
Data Synthesis ◽  
Flow Cytometric Immunophenotyping ◽  
Advantages And Disadvantages ◽  
Flow Cytometric ◽  
Study Selection ◽  
Molecular Studies ◽  
Reported Data

Abstract Objective.—Diagnostic hematopathology depends on the applications of flow cytometric immunophenotyping and immunohistochemical immunophenotyping combined with the cytomorphology and histologic features of each case. Select cases may require additional ancillary cytogenetic and molecular studies for diagnosis. The purpose of this review is to focus on the applications of flow cytometric and immunohistochemical immunophenotyping of paraffin-embedded tissue to diagnostic hematopathology. Advantages and disadvantages of these techniques are examined. Data Sources.—The literature is extensively reviewed (PubMed 1985–2003) with an emphasis on the most recent applications and those that are most useful clinically, both diagnostically and prognostically. Study Selection.—Studies were selected based on statistically significant results in large studies with reported adequate clinical follow-up. Data Extraction.—The methodology was reviewed in the selected studies to ensure reliable comparison of reported data. Data Synthesis.—Flow cytometric immunophenotyping offers the sensitive detection of antigens for which antibodies may not be available for paraffin immunohistochemical immunophenotyping. However, paraffin immunohistochemical immunophenotyping offers preservation of architecture and evaluation of expression of some proteins, which may not be available by flow cytometric immunophenotyping. These techniques should be used as complimentary tools in diagnostic hematopathology. Conclusions.—There are extensive applications of flow cytometric and immunohistochemical immunophenotyping to diagnostic hematopathology. As cytogenetic and molecular findings evolve in diagnostic hematopathology, there may be additional applications of flow cytometric and immunohistochemical immunophenotyping to this field of pathology.

scholarly journals Combining a Pharmacological Network Model with a Bayesian Signal Detection Algorithm to Improve the Detection of Adverse Drug Events

2022 ◽  
Vol 12 ◽  
Author(s):  
Xiangmin Ji ◽  
Guimei Cui ◽  
Chengzhen Xu ◽  
Jie Hou ◽  
Yunfei Zhang ◽  
...  
Keyword(s):  
Signal Detection ◽  
Network Model ◽  
Drug Safety ◽  
Adverse Drug Events ◽  
High Efficiency ◽  
Adverse Event Reporting System ◽  
Detection Algorithm ◽  
Drug Event ◽  
Statistical Approaches ◽  
Youden’S Index

Introduction: Improving adverse drug event (ADE) detection is important for post-marketing drug safety surveillance. Existing statistical approaches can be further optimized owing to their high efficiency and low cost.Objective: The objective of this study was to evaluate the proposed approach for use in pharmacovigilance, the early detection of potential ADEs, and the improvement of drug safety.Methods: We developed a novel integrated approach, the Bayesian signal detection algorithm, based on the pharmacological network model (ICPNM) using the FDA Adverse Event Reporting System (FAERS) data published from 2004 to 2009 and from 2014 to 2019Q2, PubChem, and DrugBank database. First, we used a pharmacological network model to generate the probabilities for drug-ADE associations, which comprised the proper prior information component (IC). We then defined the probability of the propensity score adjustment based on a logistic regression model to control for the confounding bias. Finally, we chose the Side Effect Resource (SIDER) and the Observational Medical Outcomes Partnership (OMOP) data to evaluate the detection performance and robustness of the ICPNM compared with the statistical approaches [disproportionality analysis (DPA)] by using the area under the receiver operator characteristics curve (AUC) and Youden’s index.Results: Of the statistical approaches implemented, the ICPNM showed the best performance (AUC, 0.8291; Youden’s index, 0.5836). Meanwhile, the AUCs of the IC, EBGM, ROR, and PRR were 0.7343, 0.7231, 0.6828, and 0.6721, respectively.Conclusion: The proposed ICPNM combined the strengths of the pharmacological network model and the Bayesian signal detection algorithm and performed better in detecting true drug-ADE associations. It also detected newer ADE signals than a DPA and may be complementary to the existing statistical approaches.

Recombinant Human Activated Protein C for Use in Severe Sepsis

2002 ◽  
Vol 36 (9) ◽  
pp. 1424-1429 ◽  
Author(s):  
David T Bearden ◽  
Cory G Garvin
Keyword(s):  
Severe Sepsis ◽  
Protein C ◽  
Drotrecogin Alfa ◽  
Data Extraction ◽  
Activated Protein C ◽  
Data Sources ◽  
Significant Advance ◽  
Controlled Clinical Trial ◽  
Control Cost ◽  
Medline Search

OBJECTIVE: To review the efficacy and safety of drotrecogin alfa (recombinant human activated protein C) in the treatment of sepsis. DATA SOURCES: Literature was identified through a MEDLINE search (1966–January 2002), the product manufacturer, and the Food and Drug Administration. STUDY SELECTION/DATA EXTRACTION: All relevant information identified from the data sources was evaluated. DATA SYNTHESIS: Drotrecogin alfa reduces coagulation and inflammation in septic patients. A large placebo-controlled clinical trial (n = 1690) of drotrecogin alfa in severely septic patients demonstrated a reduction in mortality (24.7% vs. 30.8%; p = 0.005), with increased bleeding risks (24.9% vs. 17.7%; p <0.001). Patients with more severe sepsis appeared to gain the most benefit. The complete clinical and economic impact of this agent requires further analysis. CONCLUSIONS: Drotrecogin alfa offers a significant advance in the treatment of severe sepsis. Judicious use in appropriate patients is necessary to control cost and maximize clinical benefits.

scholarly journals Using ActionADE to create information continuity to reduce re-exposures to harmful medications: study protocol for a randomized controlled trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Jeffrey P. Hau ◽  
Penelope M. A. Brasher ◽  
Amber Cragg ◽  
Serena Small ◽  
Maeve Wickham ◽  
...  
Keyword(s):  
Health Information ◽  
Adverse Drug Event ◽  
Primary Outcome ◽  
Adverse Drug Events ◽  
Primary Objective ◽  
Drug Event ◽  
Controlled Trials ◽  
Drug Reactions ◽  
Main Trial ◽  
Randomized Controlled

Abstract Background Repeat exposures to culprit medications are a common cause of preventable adverse drug events. Health information technologies have the potential to reduce repeat adverse drug events by improving information continuity. However, they rarely interoperate to ensure providers can view adverse drug events documented in other systems. We designed ActionADE to enable rapid documentation of adverse drug events and communication of standardized information across health sectors by integrating with legacy systems. We will leverage ActionADE’s implementation to conduct two parallel, randomized trials: patients with adverse drug reactions in the main trial and those diagnosed with non-adherence in a secondary trial. Primary objective of the main trial is to evaluate the effects of providing information continuity about adverse drug reactions on culprit medication re-dispensations over 12 months. Primary objective of the secondary trial is to evaluate the effect of providing information continuity on adherence over 12 months. Methods We will conduct two parallel group, triple-blind randomized controlled trials in participating hospitals in British Columbia, Canada. We will enroll adults presenting to hospital with an adverse drug event to prescribed outpatient medication. Clinicians will document the adverse drug event in ActionADE. The software will use an algorithm to determine patient eligibility and allocate eligible patients to experimental or control. In the experimental arm, ActionADE will transmit information to PharmaNet, where adverse drug event information will be displayed in community pharmacies when re-dispensations are attempted. In the control arm, ActionADE will retain information in the local record. We will enroll 3600 adults with an adverse drug reaction into the main trial. The main trial’s primary outcome is re-dispensation of a culprit or same-class medication within 12 months; the secondary trial’s primary outcome will be adherence to culprit medication. Secondary outcomes include health services utilization and mortality. Discussion These studies have the potential to guide policy decisions and investments needed to drive health information technology integrations to prevent repeat adverse drug events. We present an example of how a health information technology implementation can be leveraged to conduct pragmatic randomized controlled trials. Trial registration ClinicalTrials.gov NCT04568668, NCT04574648. Registered on 1 October 2020.

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