Clinical trials, case reports, and observational databases as sources of information on serious cancer-related adverse drug reactions (sADRs): Lessons learned from the Research on Adverse Drug Events and Reports (RADAR) project

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 19591-19591
Author(s):  
C. Bennett ◽  
K. Gleason ◽  
B. Djulbegovic ◽  
D. Raisch
Keyword(s):  
Organ Failure ◽  
Adverse Drug Reactions ◽  
Adverse Drug Events ◽  
Case Reports ◽  
Clinical Information ◽  
Lessons Learned ◽  
Sources Of Information ◽  
Drug Reactions ◽  
Fda Approval ◽  
Black Box Warnings

19591 Background: Serious adverse drug reactions (sADRs) such as venous thromboembolism resulting from cancer pharmaceutical use are underappreciated and often misattributed to the cancer diagnosis, rather than the therapy. The Research on Adverse Drug events And Reports (RADAR) group evaluated factors associated with identification of serious cancer-related sADRs (i.e. an adverse drug reaction that results in death or severe organ failure). Methods: Information on sources of clinical information, incidence, setting, and time from FDA approval to initial identification was obtained for sADRs that resulted in death or severe organ failure. Most of the ADRs are described as Black Box warnings or in “Dear Doctor” letters. Results: Summarized in table . Conclusion: Clinical trial safety reports from off-label settings facilitate identification of common (>3% rate) cancer associated sADRs. Case reports and observational databases from on-label settings facilitate detection of rare cancer-associated sADRs (<1%) often at lengthy time intervals from initial FDA approval. No significant financial relationships to disclose. [Table: see text]

Dissemination of Information on Potentially Fatal Adverse Drug Reactions for Cancer Drugs From 2000 to 2002: First Results From the Research on Adverse Drug Events and Reports Project

2003 ◽  
Vol 21 (20) ◽  
pp. 3859-3866 ◽  
Author(s):  
Lisa A. Ladewski ◽  
Steven M. Belknap ◽  
Jonathan R. Nebeker ◽  
Oliver Sartor ◽  
E. Allison Lyons ◽  
...  
Keyword(s):  
Adverse Drug Reactions ◽  
Adverse Drug Events ◽  
Package Insert ◽  
Clinical Findings ◽  
Cancer Drug ◽  
Cancer Drugs ◽  
Journal Articles ◽  
Drug Reactions ◽  
Fda Approval ◽  
First Results

Purpose: To describe the clinical findings, occurrence rates, causality evidence, and dissemination media for serious cancer drug–associated adverse drug reactions (ADRs) reported in the postmarketing setting. Methods: ADRs were termed serious if they resulted in death or severe organ failure. ADR information for oncology drugs from package insert (PI) revisions, so-called Dear Doctor letters, and journal articles was evaluated to identify serious ADRs reported from 2000 to 2002. Timing and content of information disseminated was assessed. Results: Twenty-five serious ADRs associated with 22 oncology drugs were identified after approval. Approximately half of these serious ADRs are associated with drugs approved before 1995. ADRs were described in articles in medical journals (17 ADRs), PI revisions (18 ADRs), and Dear Doctor letters (12 ADRs). PI revisions occurred less than 1 year after peer-reviewed publication for four ADRs. These revisions often differed for similar ADRs that occurred with drugs of the same class. Five of the seven ADRs lacking PI changes occurred with off-label use, for which PI change is not recommended by US Food and Drug Administration (FDA) policy. No cancer drug was withdrawn from the market during the observation period. Conclusion: Our findings demonstrate that serious ADRs may be discovered as long as 36 years after a drug receives FDA approval. This suggests a need for continued vigilance and efficient strategies for dissemination of information about ADRs associated with cancer drugs.

Post-Marketing Assessments of Serious Adverse Drug Reactions Reported by the Manufacturer to the FDA Differ Markedly with Those from an Independent Pharmacovigilance Program: Empirical Findings Based on Bisphosphonate-Associated Osteonecrosis Descriptions by the Research on Adverse Events and Reports Project and the Product Manufacturer.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3151-3151 ◽  
Author(s):  
Victoria Kut ◽  
J. Mehta ◽  
S. Singhal ◽  
C. Bennett
Keyword(s):  
Adverse Events ◽  
Adverse Drug Reactions ◽  
Single Case ◽  
Case Reports ◽  
Package Insert ◽  
Clinical Information ◽  
Comprehensive Cancer Center ◽  
Cancer Center ◽  
Drug Reactions ◽  
Post Marketing

Abstract Background: The Research on Adverse Events and Reports (RADAR) project, an independent pharmacovigilance project, has reported that post-marketing dissemination of clinical information on systemic adverse drug reactions (sADRs) in the FDA approved package labels of cancer drugs is often incomplete, delayed, or absent. Methods: We compared post-marketing clinical assessments describing one previously unreported sADR: zoledronate (Z) and pamidronate (P)-associated osteonecrosis (ON) of the jaw. Data sources included 1) information submitted to the FDA by the manufacturer in support of an FDA package insert revision, 2) RADAR investigators review of case reports of BPs associated ON of the jaw reported to the FDA MedWatch program and, 3) RADAR investigators review of medical and dental records of BP treated multiple myeloma (MM) patients with confirmed, clinically obvious ON of the jaw at a large NCI-designated comprehensive cancer center. Results: The manufacturers summary material indicated that ON occurs at a rate of &lt; 1 per 10,000 BPs treated individuals; occurs 4x more frequently in cancer versus non-cancer patients; has multiple causes including trauma, infection, radiation therapy, and long-term corticosteroids; and causal relationship with BPs is unknown. Radar investigators found that not a single case of BPs associated ON of the jaw has been reported to the FDA’s MedWatch program as of to date. RADAR investigators, however, identified 7 patients (on BPs) with confirmed ON of the jaw among 600 myeloma patients seen between March 2001 and June 2004 at our institution. Characteristics of these patients included presentation with localized jaw symptoms (n=7) requiring surgical and/or medical treatment. Conclusions: Independent toxicity assessments from the RADAR program suggest that ON is a serious, previously unrecognized ADR which can occur at a rate &gt; 1% in MM patients, appears to be causally associated with prolonged BP therapy, and is difficult to treat. In comparison, materials submitted by the manufacturer to the FDA in support of a package insert revision as well as the FDA’s MedWatch data (with 0 cases reported) indicate that this sADR is rare, has multiple etiologies, and its association with BP is unknown. The manufacturer has informed the FDA that it will conduct a retrospective single-site study to further evaluate this toxicity but this method is likely to be limited by underreporting. In contrast, our findings highlight the need for 1) a multi-site prospective study to identify the true extent of this problem in patients receiving BPs, 2) educating health care officials about the importance of reporting ADRs to the FDA MedWatch program and, 3) careful evaluation of the source of toxicity information when assessing discrepant reports of sADRs.

Recognizing Severe Adverse Drug Reactions: Two Case Reports After Switching Therapies to the Same Generic Company

2016 ◽  
Vol 11 (1) ◽  
pp. 104-108 ◽  
Author(s):  
Luca Gallelli ◽  
Giuseppe Gallelli ◽  
Giuseppe Codamo ◽  
Angela Argentieri ◽  
Andzelika Michniewicz ◽  
...  
Keyword(s):  
Adverse Drug Reactions ◽  
Case Reports ◽  
Drug Reactions ◽  
Generic Company

Differences in safety profiles of newly approved medications for multiple myeloma in real-world settings versus randomized controlled trials

2020 ◽  
pp. 107815522094193
Author(s):  
Eric P Borrelli ◽  
Conor G McGladrigan
Keyword(s):  
Multiple Myeloma ◽  
Randomized Controlled Trials ◽  
Adverse Drug Reactions ◽  
Malignant Neoplasm ◽  
Controlled Trials ◽  
Site Reaction ◽  
Drug Reactions ◽  
Infusion Site ◽  
Randomized Controlled ◽  
Fda Approval

Background Four new agents (elotuzumab, ixazomib, panobinostat, and daratumumab) were approved by the US Food and Drug Administration (FDA) in 2015 for the treatment of multiple myeloma. Our objective was to compare the safety profiles of these new medications in real-world settings and their randomized controlled trial(s). Material and methods An analysis was conducted of the FDA Adverse Event Reporting System (FAERS) for each drug consisting of the quarter that the drug received its FDA approval and the eight subsequent quarters. Reporting odds ratios and corresponding 95% confidence intervals were then calculated for each drug for each of the 10 most frequent adverse drug reactions. The randomized controlled trials that led to initial FDA approval for these medications were subsequently reviewed to assess the 10 most frequently reported adverse drug reactions in these trials. Results There were only two adverse drug reactions in the top 10 of both FAERS and its randomized controlled trials for elotuzumab (anaemia, diarrhoea) and for daratumumab (cough, back pain), five for ixazomib (diarrhoea, constipation, fatigue, nausea, peripheral neuropathy), and four panobinostat (diarrhoea, fatigue, nausea, constipation). Ixazomib had two adverse drug reactions with a significant reporting odds ratios greater than a 10-fold increased risk (plasma cell myeloma, peripheral neuropathy); elotuzumab had three adverse drug reactions (infusion site reaction, malignant neoplasm progression, deep vein thrombosis); daratumumab had three adverse drug reactions (infusion site reaction, bronchospasm, chills), while panobinostat had four (malignant neoplasm progression, decreased platelet count, diarrhoea, increased blood creatinine). Conclusion This analysis helps to highlight the importance of conducting postmarketing pharmacovigilance studies to better understand the potential adverse reactions of these medications.

scholarly journals Bibliometric analysis of adverse drug reactions and pharmacovigilance research activities in Nepal

2020 ◽  
Vol 11 ◽  
pp. 204209862092248
Author(s):  
Sunil Shrestha ◽  
Krisha Danekhu ◽  
Bhuvan KC ◽  
Subish Palaian ◽  
Mohamed Izham Mohamed Ibrahim
Keyword(s):  
Bibliometric Analysis ◽  
Adverse Drug Reactions ◽  
Case Reports ◽  
Research Performance ◽  
Case Series ◽  
Original Research ◽  
Drug Reactions ◽  
Drug Induced ◽  
Scientific Publications ◽  
Research Activities

Background: Bibliometric analyses have been used previously to study the measures of quality and impact of research performed in several health-related areas such as adverse drug reactions (ADRs) and pharmacovigilance (PV), etc. This method can assess the research performance of publications quantitatively and statistically. There is no evidence of bibilometric studies analyzing ADRs and PV from Nepal. Therefore, the present study aimed to assess scientific output on ADRs and PV-related research activities in Nepal using a bibliometric analysis of publications from 2004 January to December 2018, that is, 15 years. Methods: A systematic search was conducted in PubMed, Web of Science, Google Scholar, Scopus and Nepal Journal Online (NepJOL) databases. ‘Adverse Drug Reactions‘ or ‘ADRs‘ or ‘ADR‘ or ‘Adverse drug reaction‘ or ‘AE‘ or ‘Adverse Event‘ or ‘Drug-Induced Reaction‘ or ‘Pharmacovigilance‘ or ‘PV‘ and ‘Nepal‘. The search covered 15 years (January 2004 to December 2018) of study on ADRs and PV in Nepal. Only articles retrieved from databases were included, whereas published/unpublished drug bulletins, pharmacy newsletters and thesis were excluded. The articles thus retrieved were recorded, and thereafter analyzed. Word count code was used for the analysis of keywords used in the retrieved articles. Results: A total of 124 articles were retrieved, with the highest rate of publications in 2006 and 2007, with 16 papers each. Among the articles, 10 (8.1%) were published in Kathmandu University Medical Journal (KUMJ). Single papers were published in 38 different journals. Brief reports (1.6%), case reports (31.2%), case series (0.8%), education forums (0.8%), letters to the editor (5.6%), original research articles (41.9%), review articles (9.7%), short communications and short reports (8.1%) on ADRs and PV were recorded. Out of 124 papers, 52 (41.9%) were original research publications. The majority (74.1%) of research was done in the category of ADR incidence, types, prevention, and management, followed by policy and suggestions for strengthening national and regional pharmacovigilance centers of Nepal (14.5%). Conclusions: During the study years, there was an increase in scientific publications on drug safety. A total of 124 published articles were found during bibliometric analysis of ADRs and PV research activities in Nepal.

Quality not quantity: Key success factors from the first decade of safety reports from the Research on Adverse Drug Events and Reports project (RADAR)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 6559-6559
Author(s):  
C. Bennett ◽  
B. J. Edwards ◽  
C. C. Tigue ◽  
D. W. Raisch ◽  
D. M. Courtney ◽  
...  
Keyword(s):  
Drug Safety ◽  
Success Factors ◽  
Adverse Drug Events ◽  
Case Reports ◽  
Signal Generation ◽  
Drug Reactions ◽  
High Quality ◽  
Key Success Factors ◽  
Safety Signals

6559 Background: RADAR is the only independent academic pharmacovigilance organization funded exclusively by peer-reviewed grants. We describe the role of high quality case reports in the detection of drug safety signals. Methods: RADAR has identified 11 cancer-related adverse drug reactions (ADRs). Initial reports for small numbers of cases were obtained from our own institution, NU, (4 ADRs) or from referral centers (7 ADRs). Clinicians at these centers voluntarily provided brief case reports to RADAR, who submitted detailed case reports to the FDA/manufacturer. Clinicians were promised that patient/provider data would be kept confidential and that these data would be submitted as peer-reviewed manuscripts. Results: See Table. Conclusions: RADAR was successful at signal generation and amplification because it focused on quality, not quantity of case reports. Pharmacovigilance efforts that allow clinicians to complete brief forms, maintain confidentiality of patient and provider, and result in submission of collaborative manuscripts may improve early detection of drug safety signals initiatives in oncology. [Table: see text] No significant financial relationships to disclose.

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